Hypoxaemia is defined as an abnormally low level of oxygen in the blood (i.e., low partial oxygen tension). ^[1]

Hypoxia is defined as a condition where the oxygen supply is inadequate either to the body as a whole (generalised hypoxia) or to a specific region (tissue hypoxia). ^[1]

Why the distinction matters: You can have hypoxaemia without tissue hypoxia (mild desaturation with good cardiac output compensates), and you can have tissue hypoxia without hypoxaemia (e.g., carbon monoxide poisoning—PaO₂ is normal but O₂ delivery is impaired, or anaemia where Hb is low). Understanding this prevents you from falsely reassuring a patient with a "normal" PaO₂ who actually has impaired O₂ delivery.

Why does Type I RF have normal/low PaCO₂? In diseases causing V/Q mismatch or shunt, the patient compensates by hyperventilating. CO₂ is ~20× more diffusible than O₂ across the alveolar membrane, so hyperventilation effectively washes out CO₂ from well-ventilated regions even if those regions can't fully compensate for O₂. Hence PaCO₂ drops or stays normal, but PaO₂ remains low because O₂ diffusion is harder to compensate.

Why does Type II RF develop? When the ventilatory pump fails (CNS depression, neuromuscular weakness, chest wall disease, or severe airway obstruction), minute ventilation falls. Since alveolar ventilation is the only route for CO₂ elimination, CO₂ accumulates.

The CO₂ level in arterial blood is directly proportional to the rate of CO₂ production (VCO₂) and inversely proportional to the rate of CO₂ elimination by the lung (alveolar ventilation). Alveolar ventilation (VA) = VE × [1 − VD/VT]. Increased dead space and reduced minute ventilation are common causes of hypercapnia. ^[1]

Cellular hypoxia is a state in which there is insufficient oxygen to meet the metabolic demands of a given tissue. ^[1]

Cellular tolerance of hypoxia is variable. Skeletal muscle cells can recover fully after 30 minutes of hypoxia, but irreversible damage occurs in brain cells after only four to six minutes of similar hypoxic stress. ^[1]

Cellular mechanisms of hypoxic injury: ^[1]

1. Depletion of ATP — aerobic metabolism fails, ATP production drops, ion pumps fail
2. Intracellular acidosis — anaerobic glycolysis produces lactate
3. Increased metabolic by-products — oxygen free radicals, destruction of membrane phospholipids
4. Increased intracellular calcium — damages cytoskeleton, induces apoptosis-related genes
5. Inflammatory reaction — neutrophilic infiltration, cytokine release, free radicals, microcirculation disruption

Clinical significance: This explains why urgent correction of hypoxaemia is critical (especially for the brain), and why prolonged hypoxia leads to multi-organ failure. The 4-6 minute brain threshold is the basis for the urgency of airway management.

Respiratory distress signs: ^[1]

• Tachypnoea, respiratory rate > 20/min (normal 12-14)
• Tachycardia
• Cyanosis
• Use of accessory muscles (neck, intercostal in-sucking), gasping
• Drowsiness (hypoxia, acute CO₂ retention)
• Bradycardia, cardiac arrest (late, ominous)

Minor hypoxemia may cause few symptoms or signs. More substantial desaturation can be accompanied by increased respiratory drive (therefore tachypnea and breathlessness), increased sympathetic tone, anxiety, restlessness and sweating. Hypoxemia produces arterial vasodilation and venous constriction (related to increased sympathetic tone). ^[1]

Mild to moderate/develops slowly: Anxious, mild dyspnea, daytime sluggishness, headaches, or hypersomnolence. ^[1]

Higher levels of CO₂ or rapidly developing: Frank alterations in sensorium including delirium, paranoia, depression, and confusion, which progress to somnolence and then coma (CO₂ narcosis) as levels continue to rise. ^[1]

Severe: Asterixis, myoclonus, and seizures as well as papilledema, and dilated superficial veins. ^[1]

From the lecture slides: ^[1]

• Mental status — confusion (hypoxia), drowsiness (CO₂ retention)
• Heart rate — tachycardia (sympathetic drive); bradycardia (late/ominous)
• Respiratory rate — tachypnoea
• Respiratory pattern:
  • Rapid shallow respiratory efforts, sternal retraction, use of accessory muscles
  • Thoracoabdominal paradoxical movement — diaphragm moves cranially, abdomen moves inward with inspiration = fatiguing diaphragm working against a fatiguing load
  • Respiratory alternans — breathing alternates between predominantly abdominal and predominantly rib cage movements = sign of increased load
• Inspection of skin, lips, tongue, nail beds — cyanosis
• Pulmonary and cardiac auscultation
• Blood pressure, ECG
• Search for signs of cor pulmonale: peripheral oedema, dilated jugular veins, hepato-jugular sign ^[1]

Assess airway, breathing, circulation → ABG → ± A-a gradient → CXR → ± CT thorax/CT brain → Administer oxygen → ± Ventilatory support → Treat the underlying cause. ^[1]

Arterial blood gases: Blood taken from artery. Send to the lab in ice as soon as possible. No excessive heparin. ^[1]

Why ice? Blood cells continue to metabolise at room temperature, consuming O₂ and producing CO₂, falsely lowering PaO₂ and raising PaCO₂. Ice slows metabolism, preserving accuracy.

Why no excessive heparin? Heparin is acidic; excess dilutes the sample and falsely lowers pH, PaCO₂, and HCO₃⁻.

From the lecture ^[1]:

Step 1: pH

• Acidaemic: pH < 7.35
• Normal: 7.35–7.45
• Alkalaemic: > 7.45

Step 2: pCO₂ (Normal: 4–6 kPa)

• If elevated with acidaemia → respiratory acidosis

Step 3: HCO₃⁻ (Normal: 21–27 mEq/L)

• Metabolic status
• Renal compensation, chronicity

Expanded approach (from supporting notes): ^[2]

1. Oxygenation: PaO₂ and A-a gradient
2. Acid-base: pH
3. Primary disorder: PaCO₂ (respiratory) vs HCO₃⁻ (metabolic)
4. Compensation: expected compensation ranges
5. Anion gap (if metabolic acidosis)

The alveolar to arterial (A-a) oxygen gradient is the difference between alveolar oxygen tension (PAO₂) and arterial oxygen tension (PaO₂). ^[1]

A-a gradient = PAO₂ − PaO₂ ^[1]

PAO₂ = (FiO₂ × [Patm − PH₂O]) − (PaCO₂ ÷ R) ^[1]

Where:

• FiO₂ = 0.21 at room air
• Patm = 760 mmHg at sea level
• PH₂O = 47 mmHg at 37°C
• R = respiratory quotient = 0.8 at steady state

Normal A-a gradient = 2.5 + 0.21 × age in years ^[1]

Why it matters: A widened A-a gradient tells you the problem is in the lungs (V/Q mismatch, shunt, or diffusion impairment). A normal A-a gradient with hypoxaemia and hypercapnia points to hypoventilation (the lungs themselves are fine — the pump is failing).

Normal PaO₂/FiO₂ ratio is 300 to 500 mmHg. < 300 mmHg indicates abnormal gas exchange. < 200 mmHg indicates severe hypoxaemia. ^[1]

This is used in the Berlin criteria for ARDS ^[2]:

• Mild ARDS: 200–300 mmHg
• Moderate ARDS: 100–200 mmHg
• Severe ARDS: < 100 mmHg

A sensor is placed at a perfused thin part of the body (e.g., fingertip, earlobe). Detects pulse rate (important in determining signal quality). Emits 2 wavelengths (660 nm red, 940 nm infrared), determines absorbances due to pulsing arterial blood alone, excluding venous blood, skin, bone, muscle, and fat. ^[1]

Limitations of pulse oximetry (important for exams):

• Inaccurate in poor perfusion (shock, hypothermia, Raynaud's)
• Cannot detect CO poisoning (carboxyhaemoglobin absorbs similarly to oxyhaemoglobin at 660 nm → falsely high SpO₂)
• Cannot detect methaemoglobinaemia (reads ~85% regardless)
• Inaccurate with nail polish, excess ambient light
• Lags behind real-time changes (30-60 second delay)
• Does NOT measure PaCO₂ — a patient can have normal SpO₂ but be retaining CO₂

Arterial oxygen saturation (SpO₂ and SaO₂) ^[1]

SpO₂ (pulse oximetry) vs SaO₂ (ABG-derived) — SpO₂ is a non-invasive estimate; SaO₂ is the gold standard from ABG.

The oxygen-haemoglobin dissociation curve — sigmoid shape means:

• At high PaO₂ (> 8 kPa), Hb is nearly fully saturated → SpO₂ changes little
• At PaO₂ around 8 kPa (60 mmHg), you're on the steep part of the curve → small drops in PaO₂ cause large drops in SpO₂
• This is why PaO₂ ≤ 8 kPa is the threshold for respiratory failure — below this, O₂ delivery deteriorates rapidly

Room air contains about 21% oxygen (FiO₂ 21%). ^[1]

Prescribe the oxygen flow rate: litres/minute. Fraction of inspired oxygen (FiO₂) varies with respiratory rate and effort (variable amount of air entrainment). ^[1]

Nasal Cannula — Pros and Cons [1]

Pros: Convenient, less disfigurement. Easy to feed, allow expectoration of sputum.

Cons: FiO₂ not exact. High flow O₂ (i.e., > 6 L/min) not recommended, due to discomfort, drying of nasal passage and epistaxis (humidification needed). Dislodgement.

Dangers of oxygen: ^[1]

1. Carbon dioxide retention, especially in COPD (excessive oxygen knocks off the hypoxic respiratory drive)
2. Lung toxicity, exacerbate lung injury
3. Oxidative stress and cell injury
4. Resorption atelectasis

Resorption atelectasis explained: When breathing high FiO₂, nitrogen (normally 78% of alveolar gas) is washed out and replaced by O₂. If an airway becomes partially obstructed, the O₂ in the trapped alveolus is rapidly absorbed into blood (O₂ is much more soluble than N₂). Without N₂ to "splint" the alveolus open, it collapses.

Strong evidence (multiple controlled trials):

• COPD
• Acute cardiogenic pulmonary oedema
• Immunocompromised patients with diffuse lung infiltrates

Less strong evidence (single controlled trial or multiple case series):

• Pneumonia
• Asthma
• Postoperative respiratory failure
• Avoidance of extubation failure
• "Do not intubate" patients

Weak evidence (few case series or case reports):

• Upper airway obstruction
• Acute respiratory distress syndrome
• Trauma

NPPV is also indicated as long-term ventilatory support for patients suffering from chronic respiratory failure secondary to restrictive lung disease due to neuromuscular or chest wall disease, sleep-related breathing disorders and COPD. ^[1]

Why NPPV works in COPD exacerbation: NPPV (typically bilevel — IPAP/EPAP or BiPAP) provides inspiratory pressure support to augment tidal volume (overcoming increased airway resistance and respiratory muscle fatigue) and expiratory positive pressure to counteract auto-PEEP (intrinsic PEEP from air trapping). This improves alveolar ventilation → PaCO₂ decreases → pH improves → avoids intubation.

Why NPPV in cardiogenic pulmonary oedema: Positive pressure reduces venous return (preload) and afterload on the LV → reduces pulmonary oedema. Also recruits flooded alveoli and reduces shunt.

From the 2023 minicase Q13 (asking for two types of ventilatory support) ^[3]:

1. Non-invasive positive pressure ventilation (NPPV / NIPPV / BiPAP / CPAP)
2. Invasive mechanical ventilation (endotracheal intubation + ventilator)

This is the most commonly tested scenario integrating this lecture's content:

1. Recognise respiratory failure: tachypnoea, accessory muscle use, cyanosis, drowsiness
2. ABG: Type II RF (↓PaO₂, ↑PaCO₂, pH < 7.35, elevated HCO₃⁻ if chronic)
3. Controlled O₂: 1-2 L/min nasal cannula or 24-28% Venturi mask → target SpO₂ 88-92%
4. Repeat ABG in 30-60 minutes — if worsening acidosis/hypercapnia → NIPPV
5. NIPPV: BiPAP for Type II RF in AECOPD
6. If NIPPV fails → invasive mechanical ventilation
7. Treat underlying cause: bronchodilators (salbutamol + ipratropium nebulised), systemic corticosteroids, antibiotics if infective exacerbation ^[5]

Interpretation:

• pH 7.28 = acidaemia
• PaCO₂ 7.0 kPa = elevated → respiratory acidosis
• HCO₃⁻ 35 = elevated → metabolic compensation (renal retention of HCO₃⁻ indicates chronicity)
• PaO₂ 8.0 kPa = hypoxaemic (borderline at cutoff)
• Diagnosis: Acute-on-chronic Type II respiratory failure with partially compensated respiratory acidosis

The elevated HCO₃⁻ tells you this patient has chronic CO₂ retention (kidneys have had time to compensate by retaining HCO₃⁻), but the pH is still acidotic, meaning there's an acute decompensation on top of the chronic state.

From Felix Lai's notes ^[6] and GC 147 ^[7]:

Why 5 g/dL deoxyHb threshold? Cyanosis is detected clinically when there's enough deoxygenated Hb to produce the bluish discoloration. In anaemia (low total Hb), the patient may be profoundly hypoxic but not appear cyanotic — there isn't enough total Hb for 5 g/dL to be deoxygenated. Conversely, polycythaemia can cause apparent cyanosis at higher SpO₂.

From paediatric context but conceptually relevant ^[8]:

• Give 100% O₂ for 10 minutes
• Lung disease: PaO₂ usually exceeds 15 kPa (lungs can be recruited)
• Cyanotic CHD: PaO₂ remains relatively unchanged (blood bypasses lungs via shunt)

All of:

• Acute onset (≤ 7 days)
• Bilateral CXR opacities (not explained by effusion/collapse/nodules)
• Non-cardiogenic (PCWP < 18 mmHg)
• PaO₂/FiO₂: Mild 200-300, Moderate 100-200, Severe < 100

Chronic hypoxia → pulmonary vasoconstriction → pulmonary hypertension → right heart failure. Signs: peripheral oedema, raised JVP, hepatomegaly, hepato-jugular reflux. ECG: P pulmonale, right axis deviation, RVH.

Q1: A 70-year-old COPD patient presents with confusion and drowsiness. ABG: pH 7.25, PaCO₂ 9.0 kPa, PaO₂ 6.5 kPa, HCO₃⁻ 32 mmol/L. What type of respiratory failure? → Type II respiratory failure (low PaO₂ + high PaCO₂)

Q2: Which symptom is present in Type II but NOT Type I respiratory failure? → Headache (from CO₂-induced cerebral vasodilation) ^[4]

Q3: Hypoxaemia due to which mechanism does NOT respond to supplemental O₂? → Right-to-left shunt ^[1]

Q4: What is the target SpO₂ for a COPD patient during an acute exacerbation? → 88–92% ^[2]

Q5 (EMQ): Bilateral fine basal crackles with JVP not raised → Idiopathic pulmonary fibrosis (ILD → diffusion impairment + V/Q mismatch → Type I RF) ^[4]

Q6: Interpret an ABG: pH 7.28, PaO₂ 8.0 kPa, PaCO₂ 7.0 kPa, HCO₃⁻ 35 mmol/L. Name the clinical condition. → Acute-on-chronic Type II respiratory failure with partially compensated respiratory acidosis ^[3]

Q7: Name five physical examination findings suggesting respiratory failure. → Tachypnoea (RR > 20), tachycardia, cyanosis, use of accessory muscles, drowsiness/altered mental status ^[1][3]

Q8: Name two types of ventilatory support for respiratory failure. → NIPPV (non-invasive positive pressure ventilation) and invasive mechanical ventilation ^[1][3]

Q9: A 65-year-old COPD smoker presents with acute SOB and greenish sputum. SpO₂ 92% on room air. RR 30. What immediate management? → Controlled O₂ (target 88-92%), nebulised bronchodilators (salbutamol + ipratropium), systemic corticosteroids, antibiotics, ABG, CXR. If worsening → NIPPV.