Oxygen Transport — Tissue Delivery

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

• 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

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

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

• 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

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
• O₂ delivery 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

where

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