O2 CO2 and CO

Classifications of Hypoxia

• Low PaO2:

• Hypoxic hypoxia (low PAO2)
• Anaemic hypoxia (low O2 carrying capacity),

• Stagnant hypoxia (poor tissue perfusion)
• Histotoxic hypoxia (failure of cellular respiration)

Physiological Consequences of Hypoxaemia

Tissue Level:

• When tissue hypoxia or histotoxicity is present, the body resorts to anaerobic metabolism - 19 times less efficient than oxidative phosphorylation
• This results in depletion of high energy phosphates: ATP and phosphocreatine
• Anaerobic energy production produces H+ ions and lactate
• This produces localised acidosis - which is even worse in the CNS where these metabolites cannot escape the blood-brain barrier, causing intracellular acidosis and cell death
• Hypoxia also causes leaking of K+ outwards and Ca2+ inwards, leading to cell death

Systemic Level:

• Hypoxia detected by peripheral chemoreceptors (carotid & aortic bodies)
• Hyperventilation when PaO2 is below 55 mmHg, maximal at <30mmHg
• Secondary hypocapnia due to hyperventilation
• Hypoxic pulmonary vasoconstriction
• Increased cardiac output, decreased MAP due to systemic vasodilatation
• Preferential organ perfusion (especially brain)
• Acidosis and Hb-O2 curve right shift

Long Term:

• Increased haemaglobin/haematocrit levels due to erythropoietin

Causes of Hypercapnia/Hypocapnia

Hypercapnia

• Due to four different causes:

• Increased inspired concentration of CO2
• Increased CO2 production
• Hypoventilation
• Increased dead space

Hypocapnia

• Always due to increased alveolar ventilation, and this may be due to:

• Hypoxaemia (which drives increased ventilation at altitude)
• Metabolic acidosis compensation
• Neurological disorders (such as head injuries) and emotional states such as fear

Physiological Consequences of Hypercapnia

• Causes acidosis (in blood, ECF and CSF) via carbonic anhydrase

Neurological:

• Increased cerebral blood flow
• Increased intracranial pressure
• Increased brain pH (and metabolic dysfunction)
• Inert gas narcotic effects - similar to nitrous oxide
• Convulsant/central depressant at high levels
• Increased sympathetic outflow & increased sensitivity to parasympathetic tone via ↓ AChE activity in acidosis

Respiratory:

• Hypercapnia detected at central chemoreceptor (80% of sustained response) in the ventral medulla and in peripheral chemoreceptors (rapid response) hyperventilation up to PaCO2 of 100-150 mmHg
• Increased pulmonary vascular resistance via pulmonary vasoconstriction (weaker effect than hypoxia)
• Hypoxia (CO2 occupying space in Alv)
• Acidosis & CO2 shifts Hb-O2 dissociation curve to the right

Cardiovascular:

• Decreased heart contractility and rate (usually overridden by catecholamine release causing increased contractility and heart rate)
• Systemic vasodilation
• Arrhythmogenic

Autonomic:

• Adrenaline release during severe hypercapnia

Renal Effects:

• Arteriole constriction in severe hypercapnia (anuria)
• Renal bicarbonate compensation in respiratory acidosis and alkalosis

Physiological Consequences of Hypocapnia

• Mainly opposite effects to those of hypercapnia
• Alkalosis (↓ free Ca2+)

Neurological:

• Cerebral vasoconstriction: ↓ ICP
• ↑ neural excitability at low PaCO2

Respiratory

• Detected at central and peripheral chemoreceptors
• Reduced respiratory drive (dangerous in labour)
• Can produce apnoea in anaesthetized patients, but not usually when conscious
• Pulmonary vasodilation

Cardiovascular

• ↑ Peripheral resistance
• ↓ cardiac output
• Hb-O2 dissociation curve shifted to the left

Carbon Monoxide Poisoning

• Usually due to inhalation but may be due to ingestion of methylene chloride which is metabolised in the liver to CO
• CO binds to heme with an affinity 240 times that of O2
• It causes an allosteric change in which greatly inhibits the three other heme binding sites from offloading O2
• The result is a shift of the O2 dissociation curve to the left

• Neurological Symptoms - headache, fatigue, dizziness, convulsions, respiratory arrest
• Cardiovascular Symptoms - tachycardia, hypotension, and cardiac arrhythmia
• Gastrointestinal Symptom - Nausea
• CO also inhibits oxidative phosphorylation via cytochrome oxidase like cyanide but to a lesser extent which exacerbates the hypoxia
• The mechanism of the delayed neurological sequelae is not well understood but may be related to toxic oxygen species generated by xanthine oxidase
• Treatment is via high flow O2 and HBOT may be indicated.
• Hyperbaric oxygen therapy - given at 3x atmospheric pressure hastens the dissociation of CO from carboxyhaemoglobin and cytochrome oxidase