Canonical Question

Gas Transport – Oxygen

V5 C7.i Historical V4 F8.i 3 appearances

Master answer

O₂

Total body O2 content ~ 1.55L
- ~850mls – blood (20.4ml/100ml blood) (O2 Carriage)
  - 20.1ml/100ml – bound to Hb
  - 0.3ml/100ml – dissolved
- ~200ml – bound to myoglobin
- ~450ml in FRC
- ~50ml dissolved in tissue
O2 Content
O2 Delivery
- Determinants
O2 Extraction / Extraction Ratio

Carriage of O₂

Normal arterial blood has a PO2 of 100mmHg and is 97.5% saturated
Venous blood has a PO2 of 40mmHg and is 75% saturated
O2 is carried either bound to Hb or dissolved in solution

Dissolved O2 (2%)
- obeys Henry’s Law: amount dissolved ∝ the partial pressure.
- For each mmHg of PO2, there is 0.003ml O2/100ml blood
- therefore normal arterial blood with PO2 of 100mmHg contains 0.3ml O2/100ml

\[ C_dO_2 \; = \; a_{O_2} \; \times \; P_{O_2}\] \[ a_{O_2} \; = \; Solubility \; co-efficient \; of \, O_2 \; = \; 0.003 \, ml \, O2 \, / \, mmHg \, O_2 \, \, / \, 100 \, ml \, blood\]

Bound to Hb (98%)
- each gram of fully saturated Hb can bind 1.34ml of O2 (= Hufners constant)
- 98% O2 in blood = bound to Hb, a protein tetramer with an iron-porphyrin ring attached to each chain
- O2 coordinates with each Fe atom → inducing a conformational change → promotes binding of O2 to the other Fe atoms.
- total O2 binding capacity of Hb in blood (at normal p, temp, and PCO2) = 1.34ml/g → giving a total O2 carrying capacity of blood which an Hb of 150g/l of 20.1ml/100ml

O₂ content

\[ O_2 \; content \; = \; (O_2 \; carried \; by \; Hb) \; + \; (Dissolved \; O_2) \] \[ \; \; \; = \; (Hb \times sats \times 1.34) \; + \; (P_aO_2 \times 0.003) \]

1.34 = Hufners constant at 37 degrees
0.03 = solubility coefficient for O2 in water
O2 content per 100mL:

CaO2 (Arterial O2 content)	CvO2 (Venous O2 content)
= (15 x 1 x 1.34) + (0.003 x 100)	= (15 x 0.75 x 1.34) + (0.003 x 40)
= 20.1 + 0.3	= 15.08 + 0.12
= 20.4 ml	= 15.2 ml

Relevant Anatomy (for O2 Carriage)

RBCs
- small, flexible, biconcave discs
- cell membrane contains carbohydrate based antigens (ABO) and transmembrane proteins (Rhesus)
- No nucleus; no mitochondria (therefore aerobic metabolism not possible – entirely dependent on glucose and glycolytic pathway)
Hb: large, ion containing protein contained within RBCs
HbA
- Most common form of adult Hb (95%)
- Quaternary structure comprising 4 polypeptide globin subunits (2 alpha and 2 beta chains) in tetrahedral arrangement
- 4 globin chains held together with weak electrostatic forces
- each globin chain has its own haem group – an ion containing porphyrin ring with iron in the ferrous state (Fe²⁺)
- O₂ molecules are reversibly bound to each haem group through a weak coordinate bond to the Fe ion
- In total: 4 O2 molecules can be bound to each Hb molecule – one for each heme group
Different Hb types have different structures of globin chains
- HbA: 2 alpha, 2 beta (Adult)
- HbF: 2 alpha, 2 gamma (Foetal – replaced by HbA by 6/12 age)
- HbA2: 2 alpha, 2 delta (2-3% adults)
- Different O2 carriage and dissociation curves
Disorders of Hb synthesis:
- Decreased production of normal globin change: Thalassaemia
- Abnormal globin chains: Sickle cell anaemia
- Affects O₂ Carriage

O₂ Delivery, Uptake

O₂ Delivery and Uptake

\[ O_2 \; Delivery \; = \; Cardiac \; Output \; \times \; O_2 \; content \]

Normal O₂ Delivery = 1000ml/min
Determinents of tissue O₂ delivery
- Diffusion from alveolus to blood: Fick’s law of diffusion and factors affecting rate
- Diffusion from capillaries into tissues and cells: partial pressure difference
O₂ER: O₂ Extraction ratio = % of oxygen removed = O₂ extraction / C_aO₂

*Oxygen Delivery (DO2)*	*Oxygen Return*	*Oxygen uptake (VO2)*
= CO x Art O₂ content	= CO x Ven O₂ content	*= O₂ delivery – O₂ return*
= 5000 x 20 x 0.1	= 5000 x 15.2 x 0.1	= 1000 – 750
= 1000ml/min	= 750ml/min	= 250ml/min

Determinants of O2 Delivery

Cardiac output = HR x SV
- Pathological states like low output or hyperdynamic states can alter CO
Oxygen content dependent on Hb, Sats, PaO2
O₂delivery decreased in:
- decreased cardiac output (decreased preload, contractility, HR or increased afterload)
- decreased saturations (V/Q mismatch, decreased V, decreased PiO2, Shunt, increased CO2)
- decreased Hb (blood loss, iron deficient anaemia, anaemia of chronic disease, etc)
O₂ Uptake increased in:
- increased metabolic activity (sepsis, exercise, malignancy, pregnancy)
- right shift of HbO2 curve (CO2, ¯pH, 2,3 DPG)

HR

affected by automatic rhythmicity of cell and balance between sympathetic & parasympathetic systems

Stroke Volume

= Amount of blood pumped into the circulation per contraction
dependent on preload, contractility, afterload
Preload
- ~ Venous return
- (MSFP-RAP)/RVR
  - MSFP – Mean Systemic Filling Pressure
    Equilibration of pressures in the systemic circulation if cardiac output was abolished
    Describes the filling state of the circulation and tone of capacitance vessels
  - RAP – Right atrial pressure
  - Resistance to venous return
    - Calibre of transmitting venous system according to Poisuille-Hagen equation (where resistance ∝ 1/r⁴ )
    - Physical obstructions to venous return: Mechanical obstruction, Valvular stenosis
- Thoracic pump (negative intrathoracic pressure created during inspiration)
- Skeletal muscle pump
- One way valves
- Pump function of the ventricle
- Venous tone
- Skeletal muscle pump
- One way valves
- Pump function of the ventricle
- Venous tone
Afterload
- Proportional to aortic pressure and ventricular size
- Inversely proportional to ventricular wall thickness
- Affected by obstruction to the LVOT
Contractility
- Affected by adrenergic or muscarinic stimulation
- Availability of Ca

O2 diffusion into blood:

Fick equation:
- Describes Diffusion through tissues
- Rate of movement of solute across semi-permiable membrane J is

\[J\;={{D\;A\;\Delta C}\over{T}} \]

where

\[D=Diffusion\;constant\;\propto\;{{Solubility}\over{\sqrt{Molecular\;Weight}}}\]

C = concentration (or partial pressure for gasses)
A = cross-sectional area
T = thickness of the membrane or distance over which diffusion takes place.

Thickness of membrane (normal: 0.3μm)
Surface area of membrane (normal: 50-100m²)
- Age, posture, degree of inflation (1 mark for any)
Partial pressure gradient across membrane
- Rate of blood flow through lungs
- (no points for mentioning diffusion constant of gas – question relates to only oxygen)
Rate of oxygenation of reduced Hb
- Shift of oxygen dissociation curve (pH, temperature, PCO2, 2,3-DPG)
- Haematocrit
- Abnormalities of haemoglobin

Kerr / JC 2020

Answer by JC, Kerr

Exam appearances

Exam	Exact wording	Relationship	Success
2016A Q01	Outline the determinants of oxygen delivery to the tissues.	historical_member	—
2018A Q01	Describe the carriage of oxygen in the blood, including total oxygen delivery per minute.	historical_member	—
2026A Q02	Outline the determinants of oxygen delivery to the tissues.	safe_repeat	50.60%