Blood gases

Question 1

Explain the Bohr effect

Answer 1

• Bohr effect: states there is a decreased affinity with an increased PCO2, increased concretion of H+, increase in 2, 3DPG and higher temperatures due to denaturing the protein (need a higher level of PO2 in order to get 50% saturation)
• Decrease moves haemoglobin saturation curve right
• In tissues with a higher rate of metabolism, there is increased curve moving right so more oxygen is required
• Local metabolic rate of tissue helps match O2 delivery to its metabolic needs
• 2,3-DPG: mature red blood cells have no mitochondria and so they respire anaerobically by glycolysis, 2,3-DPG is formed as a side reaction in glycolysis and it bind to the β chains (more favourable in deoxyHb than in oxyHb) to facilitate O2 transport
• 2,3-DPG binding increase in chronic hypoxia (ventilation increases which gets rid of more CO2 - moving curve left) blood alkalosis shifts the Hb curve right, counteracting left shift of hypocapnia and alkalosis and it also helps to maintain O2 delivery to tissues
• Binding decreases under storage (blood banks) or chronic acidosis which then decrease O2 availability in transfused blood so must be stored in buffered conditions

Question 2

Explain the Haldane effect

Answer 2

• Haldane effect states: oxygenation of blood in lungs displaces CO2 from haemoglobin, increasing the removal of CO2
• Curve is plotted with large axis, but not required to look at partial pressures of up to 20kPa
• Over physiological range, curve shows a rather linear response
• Curve is relatively steep, meaning it is possible to carry more CO2 in its different forms with only having a relatively small partial pressure change
• Curve does not plateau, which means there is virtually an unlimited capacity within the physiology range that when producing more CO2, in one form or another, it can be transported (virtually unsaturable)
• At tissues, the reduction of PO2 changes affinity of binding CO2, and as O2 is given up to tissue to become deoxyHb, it is then much better at binding CO2
• Slight increase in PCO2 when going from arterial to venous so increase in CO2 content and so this extra additional increase in the CO2 content above of what would be expected of the increase of PCO2 is the Haldane effect
• Haldane effect can also be described as diffusion of O2 from blood into cells increases the affinity of haemoglobin for CO2 and H+
• Bohr and Haldane effects are reciprocal and mutually beneficial
• unloading O2 in tissue helps load CO2 (Haldane) but loading CO2 in the tissue helps unload O2 (Bohr)
• loading O2 in the lungs helps unload CO2 (Haldane) and unloading CO2 in the lungs helps load O2 (Bohr)

Question 3

What are the determinants of gas transport?

Answer 3

• Gas can either be transported over long distances by convection (pressure gradients are needed for flow) or gas exchange can occur by diffusion
• Gas exchange in lungs and tissues: diffusion of O2 and CO2 from high to low pressure occurs until capillary blood equilibrates with the gases in the alveoli or in the interstitial fluid of peripheral tissues
  1. How much of a particular gas is contained in a litre of blood
• Gas can be transported in solution (dissolved) or it can be transported bound to carrier molecules
  2. How much blood is transported
• CO is used to determine how much blood is being transported throughout body, but can look at individual tissues and see blood flow into that particular tissue
  3. Modulation of gas content in blood
• Local mechanisms to change delivery of O2 or removal of CO2 due to the local conditions through Bohr and Haldane effects
• Gas content = how much gas is contained in a litre of blood regardless of how it is carried
• Flux = litres of gas/minute transported and gas transport relates to flux and so include blood flow as well as the gas content

Question 4

Difference between gases in solution and gases bound to protein

Answer 4

• Amount of gas dissolved in solution is proportional to its partial pressure (proportionality constant is the solubility of the gas)
• Gas will only generate a partial pressure when in solution, when it is not in solution it will not contribute to the partial pressure
• Amount dissolved = partial pressure x solubility coefficient (α)
• Partial pressure is an indicator of how much gas is dissolved
• Higher CO2 solubility explains why more CO2 is dissolved in solution despite it exerting a lower partial pressure
• Concentration gradient for diffusion of gases is partial pressure gradient of each gas
• Gases can bind to the most abundant protein, Hb
• Each of the 4 subunits of Hb contain 4 haem groups and globin (peptide) chain in which each moiety of haem will bind on O2 molecules at the iron porphyrin ring
• Globin chains of adult Hb have 2 α and 2 β chains and both the α & β chains will bind CO2 and H+, will also have a role in buffering pH changes by taking up H+
• Saturation = O2 bound/ O2 capacity x 100
• O2 binding to Hb has positive cooperativity (allosteric effects) as binding to protein causes a small shape change and a small change in properties
• 1st O2 binding causes a shape change which makes it easier for 2nd O2 to bind, but when 3rd O2 binds, shape change does not make it easier for the final O2 to bind which causes a sigmoidal shape to arise for saturation/ dissociation curve
• There is resilience when loading O2 in lungs, there is also sensitivity when unloading O2 in the tissues

Question 5

O2 content and O2 consumption

Answer 5

• OxyHb dissociation is obtained by exposing blood to different partial pressures of O2 and measuring of the total O2 carrying capacity is occupied, expressed in 2 ways
  1. Saturation curve: represents % of total number of occupied ‘hooks’ for O2, but does not show amount of O2 being carried (dependent on Hb present)
  2. Content curve shows Hb present and shows curves of normal + anaemic blood differ but equally saturate at different PO2 (same P50), but amount carried is different
• Temperature and pH affect properties of Hb
• Loading and unloading conditions for blood are from arterial blood and into mixed venous blood, slope of curve is very different at these points
• O2 capacity is capacity of Hb to bind O2 if 100% saturated
  * Capacity = [Hb] x 1.39 O2/gHb
• Rate at which O2 is consumed by periphery is the difference between O2 content in arterial blood leaving heart and in mixed venous blood returning to heart
  * VO2 = (CAO2 X CO)-(CVO2 X CO)
• O2 transported = Hb bound O2 ([Hb] x capacity) + dissolved O2 (0.233 x partial pressure)
• Can increase VO2 by:
  1. If there is same O2 content per litre in arterial blood, then can extract more from that blood by desaturating blood to have a lower saturation of venous blood (this is if the tissue had a lower PO2)
  2. At the same PO2, can desaturate further by having a rightward shift Hb dissociation curve caused by products of metabolism by increasing O2 consumption
  3. Can deliver more litres per minute to the body by increasing cardiac output

Question 6

V/Q mismatch and its consequences

Answer 6

• Ventilation rate refers to volume of gas inhaled and exhaled from lungs in a given time period
  * Ventilation = tidal volume x respiratory rate (usually 6L/min)
• Perfusion is total volume of blood reaching pulmonary capillaries in given time period
• Ratio varies depending on part of lung concerned: when standing, ratio is roughly 3.3 in the apex but 0.63 in base of lung
• Ventilation exceeds perfusion towards apex, perfusion exceeds ventilation towards base
• Area of lung below heart has increased perfusion due to gravity, reducing V/Q ration
• Gravity triggers changes in 2 mechanisms:
  1. Pleural pressure: increased at base, more compliant alveoli and increased ventilation
  2. Hydrostatic pressure: decreased at apex, decreased flow and decreased perfusion
• In inadequate ventilation, V/Q reduces, and gas exchange within affected alveoli is impaired, capillary pO2 falls and pCO2 rises
• Hypoxic vasoconstriction causes diversion of blood to better ventilated parts of lung
• Haemoglobin in well ventilated alveolar capillaries will be saturated meaning RBCs will be unable to bind additional O2 to increase pO2
• pO2 level of blood remains low, acts as a stimulus to cause hyperventilation, resulting in either normal or low CO2 levels
• Mismatch in ventilation and perfusion can arise due to either reduced ventilation or reduced perfusion
• Reduced ventilation can cause respiratory failure.(type 1 or 2), pneumonia, asthma or COPD
• Reduced perfusion can cause pulmonary embolism