Respiratory acidosis

Respiratory acidosis
ICD-10	E87.2
ICD-9	276.2
DiseasesDB	95

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2]

Overview

Respiratory acidosis is acidosis (abnormal acidity of the blood) due to decreased ventilation of the pulmonary alveoli, leading to elevated arterial carbon dioxide concentration (PaCO₂).

Pathophysiology

• Metabolism rapidly generates a large quantity of volatile acid (CO₂) and nonvolatile acid. The metabolism of fats and carbohydrates leads to the formation of a large amount of CO₂. The CO₂ combines with H₂O to form carbonic acid (H₂CO₃).
• The lungs excrete the volatile fraction through ventilation, and acid accumulation does not occur.
• The PaCO₂ is maintained within a range of 39-41 mm Hg in normal states.
• A significant alteration in ventilation that affects elimination of CO₂ can cause a respiratory acid-base disorder.
• Respiratory acidosis is a clinical disturbance that is due to alveolar hypoventilation. Production of carbon dioxide occurs rapidly, and failure of ventilation promptly increases the level of PaCO₂.
• Alveolar hypoventilation leads to an increased PaCO₂ (ie, hypercapnia). The increase in PaCO₂ in turn decreases the HCO₃^-/PaCO₂ and decreases pH.
• Hypercapnia and respiratory acidosis occur when impairment in ventilation occurs and the removal of CO₂ by the lungs is less than the production of CO₂ in the tissues.

Central respiratory drive

• Alveolar ventilation is under the control of the central respiratory centers, which are located in the pons and the medulla.
• Ventilation is influenced and regulated by chemoreceptors for PaCO₂, PaO₂, and pH located in the brainstem,and in the aortic and carotid bodies as well as by neural impulses from lung stretch receptors and impulses from the cerebral cortex. Failure of ventilation quickly increases the PaCO₂.

Compensation in acute respiratory acidosis

Acute cellular compensatory stage

• The initial response is cellular buffering that occurs over minutes to hours. Cellular buffering elevates plasma bicarbonate (HCO₃^-) only slightly, approximately 1 mEq/L for each 10-mm Hg increase in PaCO₂.

Chronic renal compensatory stage

• The second step is renal compensation that occurs over 3-5 days.
• With renal compensation, renal excretion of carbonic acid is increased and bicarbonate reabsorption is increased.
• In renal compensation, plasma bicarbonate rises 3.5 mEq/L for each increase of 10 mm Hg in PaCO₂. The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows:
• Acute respiratory acidosis: HCO₃^- increases 1 mEq/L for each 10-mm Hg rise in PaCO₂.
• Chronic respiratory acidosis: HCO₃^- rises 3.5 mEq/L for each 10-mm Hg rise in PaCO₂.
• The expected change in pH with respiratory acidosis can be estimated with the following equations:
  • Acute respiratory acidosis: Change in pH = 0.008 X (40 - PaCO₂)
  • Chronic respiratory acidosis: Change in pH = 0.003 X (40 - PaCO₂)

Effect of respiratory acidosis on electrolyte

• Acidosis decreases binding of calcium to albumin and tends to increase serum ionized calcium levels.
• In addition, acidemia causes an extracellular shift of potassium, but respiratory acidosis rarely causes clinically significant hyperkalemia.

Classification

Acute respiratory acidosis

• The PaCO₂ is elevated above the upper limit of the reference range (over 6.3 kPa or 47 mm Hg)
• Accompanied with acidemia (pH <7.35)

Chronic respiratory acidosis

• The PaCO₂ is elevated above the upper limit of the reference range
• Accompanied with a normal blood pH (7.35 to 7.45) or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (HCO₃^- >30 mm Hg).

Causes

Acute

• Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs.
• This failure in ventilation may be caused by
  • Depression of the central respiratory center by cerebral disease or drugs,
  • Inability to ventilate adequately due to neuromuscular disease (eg, myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, muscular dystrophy),
  • Airway obstruction related to asthma or chronic obstructive pulmonary disease (COPD) exacerbation.

Chronic

• Chronic respiratory acidosis may be secondary to many disorders such as
  • COPD - Hypoventilation in COPD involves multiple mechanisms, including decreased responsiveness to hypoxia and hypercapnia, increased ventilation-perfusion mismatch leading to increased dead space ventilation, and decreased diaphragm function secondary to fatigue and hyperinflation.
  • Obesity hypoventilation syndrome (i.e., Pickwickian syndrome), neuromuscular disorders such as amyotrophic lateral sclerosis, and severe restrictive ventilatory defects as observed in interstitial fibrosis and thoracic deformities.
  • Lung diseases that primarily cause abnormality in alveolar gas exchange usually do not cause hypoventilation but tend to cause stimulation of ventilation and hypocapnia secondary to hypoxia. Hypercapnia only occurs if severe disease or respiratory muscle fatigue occurs.

Causes by Organ System

Cardiovascular	No underlying causes
Chemical / poisoning	Agrocide, Agronexit, Aparasin, Aphtiria, Ben-Hex, Benhexol, Benzene hexachloride, Bexol, Chloresene, Cone shell poisoning, HCH-gamma, Hexachlorocyclohexane (gamma), Lindane, Poison hemlock, Tetrodotoxin, Tick paralysis
Dermatologic	No underlying causes
Drug Side Effect	Acetylcarbromal, Alfentanil, Alprazolam, Amylobarbitone, Barbitone, Bromazepam, Brotizolam, Butabarbital, Butalbital, Butobarbitone, Camazepam, Chlordiazepoxide, Cinolazepam, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Cloxazolam, Cyclobarbital, Demethyldiazepam, Diazepam, Doxefazepam, Drug overdose, Estazolam, Ethyl loflazepate, Etizolam, Etomidate, Fentanyl, Flurazepam, Fluridrazepam, Fospropofol, General anaesthesia, Halazepam, Haloxazolam, Hexobarbital, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Mephobarbital, Methohexital, Mexazolam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Pentobarbital, Pethidine, Phenobarbital, Pinazepam, Prazepam, Primidone, Promethazine, Propofol, Quazepam, Remifentanil, Secobarbital, Sufentanil, Tapentadol, Temazepam, Tetrazepam, Thiamylal, Thiopentone, Tofisopam, Triazolam
Ear Nose Throat	No underlying causes
Endocrine	No underlying causes
Environmental	No underlying causes
Gastroenterologic	Necrotizing enterocolitis
Genetic	Athabaskan brain stem dysgenesis, Edstrom myopathy, Jeune thoracic dystrophy syndrome, Muscular dystrophy, Nemaline myopathy, Perry syndrome, Pitt-Hopkins syndrome, Ullrich congenital muscular dystrophy, X-linked myotubular myopathy, Stuve-Wiedemann syndrome
Hematologic	No underlying causes
Iatrogenic	No underlying causes
Infectious Disease	Clostridium tetani, Poliomyelitis
Musculoskeletal / Ortho	Cervical spine injury, Congenital diaphragmatic hernia, Congenital fiber-type disproportion myopathy, Diaphragm paralysis, Idiopathic spinal scoliosis, Rib fracture, Severe kyphoscoliosis, Stuve-Wiedemann syndrome, Muscular dystrophy, Nemaline myopathy, Ullrich congenital muscular dystrophy, X-linked myotubular myopathy, Neuromuscular diseases, Myasthenia gravis, Polymyositis
Neurologic	Amyotrophic lateral sclerosis, Brain death, Brown-Vialetto-van Laere syndrome, Central sleep apnea, CNS depression, Congenital failure of autonomic control, Guillain-Barre syndrome, Motor neuron disease, Neuromuscular diseases, Raised intracranial pressure, Subacute necrotising encephalomyelopathy, X-linked infantile spinal muscular atrophy, Athabaskan brain stem dysgenesis, Diaphragm paralysis
Nutritional / Metabolic	Subacute necrotising encephalomyelopathy
Obstetric/Gynecologic	No underlying causes
Oncologic	No underlying causes
Opthalmologic	No underlying causes
Overdose / Toxicity	Acetylcarbromal, Alfentanil, Alprazolam, Amylobarbitone, Barbitone, Bromazepam, Brotizolam, Butabarbital, Butalbital, Butobarbitone, Camazepam, Chlordiazepoxide, Cinolazepam, Clobazam, Clonazepam, Clorazepate, Clotiazepam, Cloxazolam, Cyclobarbital, Demethyldiazepam, Diazepam, Doxefazepam, Drug overdose, Estazolam, Ethyl loflazepate, Etizolam, Etomidate, Fentanyl, Flurazepam, Fluridrazepam, Fospropofol, General anaesthesia, Halazepam, Haloxazolam, Hexobarbital, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Mephobarbital, Methohexital, Mexazolam, Midazolam, Nitrazepam, Oxazepam, Oxazolam, Pentobarbital, Pethidine, Phenobarbital, Pinazepam, Prazepam, Primidone, Promethazine, Propofol, Quazepam, Remifentanil, Secobarbital, Sufentanil, Tapentadol, Temazepam, Tetrazepam, Thiamylal, Thiopentone, Tofisopam, Triazolam, Oxygen
Psychiatric	No underlying causes
Pulmonary	Chronic bronchitis, Chronic obstructive pulmonary disease, Emphysema, Foreign body in respiratory tract, Hyaline membrane disease, Obesity hypoventilation syndrome, Obstructive sleep apnea, Pickwickian syndrome, Pneumothorax, Pulmonary hypoplasia, Respiratory depression, Respiratory distress syndrome, Severe asthma, Shallow Breathing , Snoring, Stuve-Wiedemann syndrome, Tracheal stenosis
Renal / Electrolyte	No underlying causes
Rheum / Immune / Allergy	Myasthenia gravis, Polymyositis, Guillain-Barre syndrome
Sexual	No underlying causes
Trauma	Flail chest, Cervical spine injury, Pneumothorax
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Asphyxiation, Reduced level of consciousness, Congenital failure of autonomic control, Shallow Breathing

Causes in Alphabetical Order

Acetylcarbromal Agrocide Agronexit Alfentanil Alprazolam Amylobarbitone Amyotrophic lateral sclerosis Aparasin Aphtiria Asphyxiation Athabaskan brain stem dysgenesis Barbitone Ben-Hex Benhexol Benzene hexachloride Bexol Brain death Bromazepam Brotizolam Brown-Vialetto-van Laere syndrome Butabarbital Butalbital Butobarbitone Camazepam Central sleep apnea Cervical spine injury Chlordiazepoxide Chloresene Chronic bronchitis Chronic obstructive pulmonary disease Cinolazepam Clobazam Clonazepam Clorazepate Clostridium tetani Clotiazepam Cloxazolam CNS depression Cone shell poisoning Congenital diaphragmatic hernia Congenital failure of autonomic control Congenital fiber-type disproportion myopathy Cyclobarbital Demethyldiazepam Diaphragm paralysis Diazepam Doxefazepam Drug overdose Edstrom myopathy Emphysema Estazolam Ethyl loflazepate Etizolam Etomidate Fentanyl Flail chest Flurazepam Fluridrazepam Foreign body in respiratory tract Fospropofol General anaesthesia Guillain-Barre syndrome Halazepam Haloxazolam HCH-gamma Hexachlorocyclohexane (gamma) Hexobarbital Hyaline membrane disease

Idiopathic spinal scoliosis Jeune thoracic dystrophy syndrome Ketazolam Lindane Loprazolam Lorazepam Lormetazepam Medazepam Mephobarbital Methohexital Mexazolam Midazolam Motor neuron disease Muscular dystrophy Myasthenia gravis Necrotizing enterocolitis Nemaline myopathy Neuromuscular diseases Nitrazepam Obesity hypoventilation syndrome Obstructive sleep apnea Oxazepam Oxazolam Oxygen Pentobarbital Perry syndrome Pethidine Phenobarbital Pickwickian syndrome Pinazepam Pitt-Hopkins syndrome Pneumothorax Poison hemlock Poliomyelitis Polymyositis Prazepam Primidone Promethazine Propofol Pulmonary hypoplasia Quazepam Raised intracranial pressure Reduced level of consciousness Remifentanil Respiratory depression Respiratory distress syndrome Rib fracture Secobarbital Severe asthma Severe kyphoscoliosis Shallow Breathing Snoring Stuve-Wiedemann syndrome Subacute necrotising encephalomyelopathy Sufentanil Tapentadol Temazepam Tetrazepam Tetrodotoxin Thiamylal Thiopentone Tick paralysis Tofisopam Tracheal stenosis Triazolam Ullrich congenital muscular dystrophy X-linked infantile spinal muscular atrophy X-linked myotubular myopathy

Differential diagnosis of respiratory acidosis

For differential diagnosis of respiratory acidosis is consideration of the three structures involved in ventilation should be made: the chest cavity, central respiratory drive, and the lungs and airways.

Lung and airway

• Pneumonia
• Pulmonary edema
• COPD/Asthma
• Foreign body
• Tumor

Chest cavity

• Neuromuscular disorder
• Muscular disorder
• Kyphoscoliosis
• Pleural effusion
• Flail chest
• Pneumothorax

Central respiratory drive

• Obstructive sleep apnea
• Sedation
• Narcotics
• Respiratory drive hypofunction secondary to infection, inflammation or infarction