Breathing Control: Hypoxia, Hypercapnia and Ventilation

• The presentation covers the control of breathing in relation to hypoxia.

Key Terms

• SPO2: Oxygen level in the blood measured by oximetry.
• SO2: Oxygen saturation in the blood.
• PAO2: Oxygen level in the alveoli.
• PaO2: Oxygen level in arterial blood.
• A-a Gradient: The difference between PAO2 and PaO2, ideally less than 12.

Definitions

• Hypoxia: A fall in alveolar, leading to a fall in arterial pO2.
• Hypercapnia: A rise in alveolar, leading to a rise in arterial CO2.
• Hypocapnia: A fall in alveolar, leading to a fall in arterial CO2.
• Hyperventilation: Increased ventilation without a change in metabolism.
• Hypoventilation: Decreased ventilation without a change in metabolism.

Effects of Hyperventilation and Hypoventilation on Plasma pH

• pCO2 affects plasma pH, according to the Henderson-Hasselbalch equation.
• High pCO2 leads to low pH, resulting in acidosis.
• The pH equation: pH = 6.1 + log ([HCO3-] / (pCO2 x 0.23))

Hyperventilation

• Hyperventilation leads to hypocapnia and respiratory alkalosis.
• pH rises above 7.6 during hyperventilation.
• Reduced free calcium can cause fatal tetany due to calcium's decreased solubility in rising pH levels, leading to nerve excitability.

Hypoventilation

• Hypoventilation leads to hypercapnia and respiratory acidosis.
• pH decreases during hypoventilation.
• Can cause enzymes to denature.

Respiratory Acidosis

• CO2 is produced more rapidly than it is removed via hypoventilation.
• Alveolar pCO2 rises, leading to a greater increase in dissolved CO2 than HCO3-, decreasing plasma pH.

Compensated Respiratory Acidosis

• Respiratory Acidosis persists, the kidneys reduce HCO3- excretion in response to low pH, resulting in a pH just below 7.3.

Respiratory Alkalosis

• CO2 is removed from the alveoli more rapidly than is produced via hyperventilation.
• Alveolar pCO2 decreases, increasing plasma pH.

Compensated Respiratory Alkalosis

• Respiratory Alkalosis persists, and the kidneys excrete HCO3- in response to high pH, restoring the ratio of dissolved CO2 to HCO3-.

Metabolic Acidosis

• Metabolic acid production displaces HCO3- from plasma as the acid is buffered, decreasing blood pH.

Compensated Metabolic Acidosis

• The ratio of dissolved CO2 to HCO3- is restored by lowering pCO2; the lungs increase ventilation to correct pH.

Metabolic Alkalosis

• Plasma HCO3- rises, increasing blood's pH.

Compensated Metabolic Alkalosis

• The ratio of dissolved CO2 to HCO3- may be restored to near normal by raising pCO2, and the lungs decrease ventilation to correct pH.

Factors Affecting Ventilation: Falling Inspired pO2

• Peripheral chemoreceptors in the carotid and aortic bodies detect falling arterial pO2.
• The carotid and aortic bodies are stimulated by decreased oxygen supply relative to their oxygen usage and only respond to large drops in O2.
• Stimulation of the receptors increases tidal volume, respiration rate, blood flow to the brain, blood flow to kidneys, and heart pumping.

Factors Affecting Ventilation: Increased Inspired pCO2

• Peripheral chemoreceptors in the carotid and aortic bodies detect changes in pCO2 but are insensitive.
• Central chemoreceptors in the medulla are more sensitive and alter breathing.
• A small rise in pCO2 increases ventilation, and a small fall in pCO2 decreases ventilation.

Central Chemoreceptors and CSF

• Central chemoreceptors respond to cerebrospinal fluid (CSF) pH changes.
• The blood-brain barrier separates the CSF from the blood: CSF pCO2 is determined by arterial pCO2, but HCO3- and H+ cannot cross.
• CSF [HCO3-] is controlled by choroid plexus cells.
• CSF pH is determined by the ratio of [HCO3-] to pCO2.
• In the short term, [HCO3-] is fixed, so pCO2 drops raise pH, and pCO2 rises lower pH.
• Choroid plexus cells compensate for persisting changes by altering CSF [HCO3-].

Respiratory Failure

• Respiratory failure is the failure to achieve adequate O2 for tissue and metabolic requirements.
• Type 1 Respiratory Failure: Respiratory rate increases, pO2 decreases, and CO2 remains normal or increases.
• Type 2 Respiratory Failure: Respiratory rate increases, pO2 decreases, and CO2 increases.
• Type 3 Respiratory Failure: Postoperative.
• Type 4 Respiratory Failure: Due to increased requirements in a hyper-dynamic state.

Mechanism of Hypercapnea

• Hypercapnea is caused by hypoventilation, since CO2 is a highly diffused gas.

Hypoxia

• Hypoxia occurs when there is a fall in alveolar, thus arterial pO2.
• Arterial pO2 falls below 8kPa breathing air at sea level.
• Type 1 Respiratory Failure: Arterial hypoxia with normal or low pCO2, causing breathlessness, exercise intolerance, and central cyanosis.
• Type 2 Respiratory Failure: Arterial hypoxia with elevated pCO2.

Mechanisms of Hypoxia

• Low pO2 in inspired air occurs even when everything else is normal.
• Hypoventilation is always associated with increased pCO2 (Type 2 Respiratory Failure).
• Central causes include respiratory depression due to opiate overdose and head injury
• Neuromuscular problems include myasthenia gravis.
• Muscle weakness (NMJ/Nerve/Muscle).
• Chest wall problems (mechanical) include scoliosis/kyphosis, morbid obesity, trauma, and pneumothorax.
• It can be linked to hard-to-ventilate lungs:
• Airway obstruction
• COPD and asthma when the airway narrowing is severe and widespread
• Severe fibrosis

Diffusion Impairment

• O2 diffuses less readily than CO2, so pCO2 is low/normal with a wide A-a gradient.
• Structural changes of the lungs cause hypoxia.
  • Lung fibrosis causes thickening of the alveolar capillary membrane
• Increased path length in Pulmonary Oedema.
• Reduced total area for diffusion
• Emphysema

Ventilation Perfusion Mismatch

• Most common hypoxia mechanism, O2 diffuses less readily than CO2 (pCO2 is low/normal with wide A-a gradient).
• Always Type 1 Respiratory Failure.
• Reduced ventilation of some Alveoli (Lobar Pneumonia).
• Reduced perfusion of some Alveoli (Pulmonary Embolism).

Shunt

• Oxygen affection is more with wide A-a gradient.
• Abnormal Right to Left Shunts bypass the gas exchange areas.
• Cyanotic Heart Diseases (VSD)
• Extra-cardiac shunt as in tetralogy of Fallot.
• Plumonary shunt (AVM).

Explore the relationship between breathing control and hypoxia including key terms like SPO2, SO2, PAO2, and PaO2. Understand the effects of hyperventilation and hypoventilation on plasma pH, and the roles of pCO2 and the Henderson-Hasselbalch equation.