Also see ABG Interpretation

Oxygen Transport

Oxygen is carried within the circulation bound to Hb (98%) and dissolved in plasma (2%)

O X_{2} content per 100 mL of blood = O X_{2} bound to haemoglobin H \overset{u}{¨} fner’s constant 1.34 \times [Hb] \times \frac{S _{a} O X _{2}}{100%} + O X_{2} dissolved in blood Solubility constant 0.023 \times P_{a} O X_{2} \approx 19.8 mL for typical arterial blood

Very little $O X_{2}$ is stored in the body ⇒ apnoea rapidly leads to hypoxia

Red Blood Cells

Do not contain a nucleus or mitochondria ⇒ entirely dependent on glucose and the glycolytic pathway for energy

Haemoglobin

HbA has two $α$ -chains and two $β$ -chains each of which have an iron-containing porphyring ring with iron in the ferrous state ( $Fe X^{2 +}$ )
Haemoglobin has a preference to be either fully saturated or desaturated due to cooperativity
- Cooperative binding is the increase in $O X_{2}$ affinity of Hb with each successive $O X_{2}$ binding
Rightward shift (↑ offloading) of the oxyhaemoglobin dissociation curve is caused by (mnemonic: CADETS):
- Increased $P CO X_{2}$
- Acidosis
- Increased 2,3-dihosphoglycerate
- Exercise
- Increased temperature
- The presence of sickle haemoglobin (HbS) in sickle cell disease

Types of Hb

Physiological
- $HbA$ : normal most common form ( $α X_{2} β X_{2}$ )
- $HbA X_{2}$ : other adult form accounting for 2-3% ( $α X_{2} δ X_{2}$ )
- $HbF$ : normal variant during feotal life and has a higher affinity for $O X_{2}$ ( $α X_{2} γ X_{2}$ )
Pathological
- $HbS$ : in sickle cell disease which has an abnormal $β$ -globin subunit
- $MetHb$ : Methaemoglobinaemia is where the ferrous iron within the Hb molecule is oxidised to ferric iron ( $Fe X^{3 +}$ ); $Fe X^{3 +}$ cannot bind to $O X_{2}$ , so $MetHb$ cannot participate in $O X_{2}$ transport
  - Low level of $MetHb$ is maintained by:
    - Glutathione/nicotinamide adenine dinucleotide phosphate (NADPH) system where oxidising agents are reduced by glutathione before being able to oxidise ferrous iron; the pentose phosphate pathway is integral for this as it supplies NADPH to return glutathione back to its reduced form
    - $MetHb$ reductase/nicotinamide adenine dinucleotide (NADH) system reduces ferric iron by a reduction system involving $MetHb$ reductase
  - Methaemoglobinaemia occurs as a result of:
    - Oxidising agents overwhelming the glutathione system (e.g. suphonamide antibiotics, nitric oxide and prilocaine)
    - Failure of protective reduction systems (e.g. G6PD deficiency)
  - Pulse oximeters misread $MetHb$ and display values of 85% irrespective of $MetHb$ concentration
  - Manage with supplemental oxygen in mild cases and methylene blue in severe cases
- $COHb$ : Formed when $Hb$ binds inhaled carbon monoxide molecules
- $CyanoHb$ : Cyanohaemoglobin is formed when $Hb$ is exposed to cyanide ions

Carbon Dioxide Transport

A typical adult produces $CO X_{2}$ at a basal rate of 200mL/min; during exercise it can increase as high as 4000 mL/min
$CO X_{2}$ is transported in circulation in three forms
- Dissolved in plasma
- Bound to Hb and other proteins as carbamino compounds
  - When $CO X_{2}$ reacts with a terminal amine group within the Hb molecule forming carbaminohaemoglobin
  - Deoxyhaemoglobin forms carbamino compounds more readily than oxyhaemoglobin
- Bicarbonate
  - Carbonic anhydrase catalyses the reaction to form bicarbonic acid
    - The cytoplasm of red blood cells contains carbonic anhydrase, but plasma does not contain carbonic anhydrase therefore it can only occur within the RBC
    - Almost all $H X_{2} CO X_{3}$ dissociates into $HCO X_{3} X^{-}$ and $H X^{+}$
    - $CO X_{2}$ and water can diffuse directly through the RBC membrane whilst $H X^{+}$ and $HCO X_{3} X^{-}$ cannot; forward direction of the reaction is maintained by preventing the build up $HCO X_{3} X^{-}$ and $H X^{+}$ via two processes:
      - Chloride shift (Hamburger effect): $HCO X_{3} X^{-}$ is transported across teh RBC membrane down its electrochemical gradient by the $Cl X^{-}$ / $HCO X_{3} X^{-}$ exchanger
      - Binding of $H X^{+}$ to histidine side chains of the haemoglobin molecule reducing intracellular concentration of $H X^{+}$

CO X_{2} + H X_{2} O CA H X_{2} CO X_{3} H X^{+} + HCO X_{3} X^{-}

Haldane Effect

Describes the observation that deoxyhaemoglobin is more effective net carrier of $CO X_{2}$ than oxyhaemoglobin
This is because of two reasons:
- Deoxyhaemoglobin more readily forms carbamino compounds
- Deoxyhaemoglobin is a stronger base than oxyhaemoglobin and more readily accepts $H X^{+}$ allowing rightward shift of the above equilibrium (increasing $HCO X_{3} X^{-}$ formation)
Metabolically active tissues produce $H X^{+}$ and $CO X_{2}$ . Through the Bohr effect and its effect on $P_{50}$ , additional $O X_{2}$ is offloaded to the most metabolically active tissues
- According to the Haldane effect, the newly formed deoxyhaemoglobin is better at binding $H X^{+}$ and carrying $CO X_{2}$ than is oxyhaemoglobin
- The metabolic waste products are therefore efficiently transported away from the tissues to the lungs

Carbon Dioxide Dissociation Curve

Describes the relationship between partial pressure of $CO X_{2}$ ( $P CO X_{2}$ ) and the blood $CO X_{2}$ content
Typical $P_{a} CO X_{2}$ is 5.3 kPa (~39.8 mmHg) and results in a $CO X_{2}$ content of about 48 mL/100 mL
Typical $P_{v} CO X_{2}$ is 6.1 kPa (~45.8 mmHg) and results in a $CO X_{2}$ content of about 52 mL/100 mL
At physiological $P CO X_{2}$ , the $CO X_{2}$ dissociation curve is essentially linear
Often drawn as two curves representing arterial and venous blood

Importance of Pre-Oxygenation During Intubation

In total, the circulation and lungs contain approximately 2.5 L of immediately available $CO X_{2}$ and 1550 mL of $O X_{2}$ . If a healthy patient stops breathing (e.g. on induction of general anaesthesia), basal processes will continue: 250 mL/min of $O X_{2}$ will be consumed and 200 mL/min of $CO X_{2}$ will be produced. Therefore: $P CO X_{2}$ will increase by 0.4–0.8 kPa/min. $P O X_{2}$ will fall. The rate of fall is complicated, involving factors such as Hb concentration and total blood volume. Typically, $S_{a} O X_{2}$ falls to 70% ( $P O X_{2}$ 5.0 kPa) after 2 min. However, if the patient breathes $O X_{2}$ for sufficient time to completely de-nitrogenate their functional residual capacity prior to the period of apnoea, the quantity of stored $O X_{2}$ increases to over 3 L – even after 5 min of apnoea, $S_{a} O X_{2}$ will remain at 100%. Basal metabolic processes will continue and after 5 min the $P_{a} CO X_{2}$ will approach 10 kPa.

Lung Mechanics

Definitions

$\dot{V} = V_{T} \times Respiratory Rate$

Where:
- $\dot{V}$ is the minute ventilation
- $V_{T}$ is the tidal volume $\dot{V}_{A} = (V_{T} - V_{D}) \times Respiratory Rate$
Where:
- $\dot{V}_{A}$ is the alveolar ventilation
- $V_{D}$ is teh physiologic dead space $Compliance = \frac{Δ Volume}{Δ Pressure}$ $Q = \frac{Δ P}{R}$
Where
- $Q$ is airflow
- $Δ P$ is pressure gradient
- $R$ is airway resistance

Source

Chambers, D., Huang, C., Matthews, G., 2019. Basic Physiology for Anaesthetists, 2nd ed. Cambridge University Press. https://doi.org/10.1017/9781108565011

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Table of Contents

Respiratory Physiology

Oxygen Transport

Red Blood Cells

Haemoglobin

Types of Hb

Carbon Dioxide Transport

Haldane Effect

Carbon Dioxide Dissociation Curve

Lung Mechanics

Definitions

Source

Recent Notes

Sepsis

Pressors

Heart Failure

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