Respiratory Physiology - Oxygen Transport Flashcards
https://academic.oup.com/bjaed/article/16/10/341/2288629
What are the arterial, venous and P50 points on the oxyhaemoglobin dissociation curve for HbA?
Arterial point - SO2 97-100%, 13.3 kPa
Venous point - SO2 75%, 5.3 kPa
P50 - SO2 50%, usually 3.5kPa
Describe the oxyhaemoglobin dissociation curve, and explain how it compares to HbF and Myoglobin.
HbA is a sigmoid graph as a result of co-operative binding.
HbF is a sigmoid graph to the left of Hba, reflective of its higher affinity for O2. (P50 is 2.5 kPa)
Mb is a hyperbolic graph, to the far left of both types of haemoglobin. It can only carry one molecule of O2.
What conditions shift the Oxyhaemoglobin dissociation curve to the right?
Technically measured using the P50
Right shift (Lower affinity for O2)
-Acidosis/High CO2 (Bohr Shift)
-Hyperthermia
-Increased 2, 3-DPG
-Pregnancy
-Altitude
-HbS
What conditions shift the Oxyhaemoglobin dissociation curve to the left?
Technically measured using the P50
Left shift (Higher affinity for O2)
-Alkalosis/Low CO2
-Hypothermia
-Reduced 2, 3-DPG
-Carbon Monoxide
-Methaemoglobinaemia
-HbF
Describe the Bohr Effect
A reduction in pH reduces the affinity of Hb for O2, and shifts the dissociation curve to the right.
An increase in PaCO2 (and thus dissolved carbonic acid), is a substantial driver of this.
It ensures sustained oxygen delivery to the most hypoxic tissues at the distal end of the capillary bed.
Relative alkalosis in the lungs (as PaCO2 drops), encourages uptake of O2.
Define the oxygen cascade
The oxygen cascade is a stepwise reduction in partial pressure of oxygen between the atmosphere and the mitochondrion via the cardiorespiratory systems that allow oxygen to move down its partial pressure gradient
What equations and steps make up the oxygen cascade
- Partial pressure of oxygen in room air
PO2 = FiO2 x Patm21% x 101kPa = 21kPa - As air enters the trachea, it is warmed and humidified. The PO2 drops due to the saturated vapour pressure of water.
PO2 = FiO2 x (Patm-PH2O)21% x (101kPa-6kPa) = 19.95kPa - Air travels down from the trachea, to bronchioles, to alveoli, where it mixes with CO2. This gives us the alveolar gas equation:
PAO2 = FiO2 x (Patm-PH2O) - PaCO2/Respiratory quotient21% x (101kPa-6kPa) - 5.3kPa/0.8 = 13.3kPa - PaO2 drops due to the diffusion barrier into the pulmonary capillaries, and again due to physiological and anatomical shunts, to form arterial blood.
This classically reduces PaO2 by approximately 0.5-1.0kPa - Oxygen is steadily consumed through arteries, arterioles and capillaries, finally diffusing to the mitochondria, with a final partial pressure of 1.5kPa.
Respiratory quotient - Proportion of CO2 produced compared to O2 used, varies by substrate (Carb/Fat/Protein)
Physiological Shunts - Thebesian and Bronchial Veins (2% of blood)
Anatomical Shunts - VQ mismatch, AVMs
Patm - Atmospheric pressure
PO2 - Partial pressure of O2
PAO2 - Alveolar partial pressure of O2
PaO2 - Arterial partial pressure of O2
What is the Pasteur Point?
The minimum partial pressure of Oxygen at which oxidative phosphorylation is still able to occur.
Around 0.13kPa (1mmHg)
What is oxygen flux (DO2), how is it calculated, and how can it be affected?
A term used to describe the flow and consumption of oxygen into and throughout the bodyOxygen Flux = Cardiac Output x Arterial Oxygen Content
CO: Stroke Volume x Heart Rate
CaO2: Carried Oxygen + Dissolved Oxygen
Changing any of these 4 parameters affects oxygen flux
Stroke Volume (SV) - Preload, inotropy or afterload
Heart Rate (HR) - Chronotropy
Carried Oxygen - Change Hb or saturation of available Hb
Dissolved Oxygen - Change FiO2 or VQ matching
How is the oxygen content of arterial blood estimated?
The content of Oxygen in arterial blood is made up of the amount bound to haemoglobin, and the amount dissolved in plasma.CaO2 = (Hb x Saturation x Huffner's Constant) + PaO2 x 0.23ml/L(150g/L x 97% x 1.34ml) + (13.3kPa x 0.23ml/L) = 198.029ml/L
What is critical DO2?
The minimum oxygen delivery that can meet the body’s oxygen consumption demand.
Variable, but approximately 4-8ml/kg per minute
What is the Oxygen extraction ratio?
The proportion of oxygen delivered by the blood that is taken up into the tissues. Expressed as VO2/DO2.
Normally around 0.25 - leaving a significant ‘buffer’ of spare oxygen for a sudden decrease in supply, or increase in metabolic demand.
The heart is sensitive to ischaemia as it has an oxygen extraction of around 0.7 at rest, relying on increased perfusion rather than increased oxygen extraction to satisfy any increase in demand.
How does Oxygen Content in the blood change with altitude?
As altitude increases, the partial pressure of oxygen decreases.
Although the FiO2 is still 21%, ambient pressure decreases, so the partial pressure of available oxygen also decreases, reducing the PO2 in the first step of the oxygen cascade.
PO2 = FiO2 x Patm
What are the effects of altitude on cardiovascular physiology?
Hypoxic pulmonary vasoconstriction increases Pulmonary vascular resistance, and right ventricular afterload, can lead to pulmonary oedema.
Increased HR from sympathetic stimulation
Pressure diuresis and respiratory losses due to hyperventilation reduce plasma volume, preload, and thus stroke volume. EPO production further increases Hct.
Increases Hct and blood viscosity, with higher workload for the myocardium and increased thrombotic risk.
What are the effects of altitude on respiratory physiology?
Reduced PaO2 increases TV and RR, causing a reduction in PaCO2, and increasing PAO2 via the alveolar gas equationPAO2 = FiO2 x (Patm-PH2O) - PaCO2/Respiratory quotient
Eventually results in the respiratory braking effect - the resultant alkalosis (via central chemoreceptors) and hypocapnoea (via peripheral chemoreceptors) limits MV.
Alkalosis causes left shift of the oxygen dissociation curve, stimulating production of 2,3-DPG, shifting it rightwards again.
As part of acclimatisation, the kidneys compensate by generating a compensatory metabolic acidosis, allowing further hyperventilation, and shifting the oxygen dissociation curve rightwards again.
