Oxygen Transport Flashcards
How much ATP does glucose produce aerobically and anaerobically?
Aerobic: ~38 ATPs
Anaerobic: 2 ATPs
How does oxygen get to tissues and then, how is it used?
Blood carries O2 to tissues
O2 delivery must match utilisation
O2 travels to tissues down the “oxygen cascade”
How does the oxygen cascade work?
As O2 moves from the atmosphere, to the alveoli/capillaries + then to mitochondria of tissues, O2’s partial pressure will drop so O2 will travel down this cascade
The O2 difference at the alveolar arterial is usually small but may be increased in lung disease
What would happen if dissolved oxygen was the only method of transport to tissues?
Resting O2 consumption is 250ml/min + it has poor solubility in water (~3ml/L dissolved at alveolar pO2 of 13.3 kPa)
So tissues would need to be supplied with > 80L/min blood at rest when CO ~5L/min
What is oxygen binding? What are the problems with it?
Chemical reaction needed to transport more O2 per L of blood; many substances react with O2 so getting it into blood is not hard BUT extracting sufficient amounts at tissue level is the challenge so this requires a rapidly reversible reaction that can respond to wide range of demand
What is haem?
Porphyrin compound coordinated to a Fe atom (in ferrous form; Fe2+)
Binds O2 reversibly in blood + goes red when fully saturated or purple when unbound
What is haemoglobin?
A tetramer made up of 2 α + 2 β globin chains - each coiled polypeptide chain has 1 haem + 1 globin component -> quaternary structure
Hb A = main adult form
What is the relevance of haemoglobins structural features?
Structure influenced by various inputs + its modification alters the O2 affinity of the molecule
What are the 2 forms haemoglobin can exist as?
Relaxed: open + receptive structure allowing O2 to access haem groups = higher O2 affinity
Tense: inhibits O2 binding so binds O2 500x less avidly than in relaxed form
What happens to haemoglobins configuration when there is low environmental pO2?
Hb is in its tense form + no O2 is bound as it is hard to bind the 1st O2 molecule - initial binding requires a threshold minimum pO2
What happens to haemoglobins configuration when environmental pO2 starts to rise?
As Hb binds O2 to 1 chain, its structure is modified + open becoming the relaxed form so binding next O2 molecule is easier + reflects cooperativity between O2 binding sites -> binding becomes easier as more O2 is bound
What is the dissociation curve?
Represents the reversibility of O2 binding
X axis = pO2 (kPa/mmHg)
Y axis = % of total amount of O2 bound at full saturation
Total O2 content = bound + dissolved (ml of O2/dL of blood)
What is O2 saturation?
As shown by dissociation curve, chemical binding becomes saturated/plateaus above given pO2
Amount of O2 bound then depends on how much Hb is available however, saturation is INDEPENDENT of [Hb]
What happens to the bloods O2 saturation + concentration in anaemia?
O2 saturation remains the SAME
Less [Hb] so less [O2]
What can the O2 dissociation curve reveal?
How much O2 will be bound/given up when blood is moved between areas with different pO2’s e.g. from lungs to tissues or vice versa
Why does the O2 dissociation curve have its typical sigmoid shape?
At first, relationship between pO2 + binding is poor
Binding changes configuration, increasing O2 affinity + facilitates further binding so curve steepens rapidly as pO2 rises
Saturation then occurs so the curve will level out + plateau
What are the O2 dissociation curve anchor points?
1 kPa pO2 = Hb virtually unsaturated
3.5 kPa pO2 = Hb half saturated
8 kPa pO2 = Hb almost fully saturated e.g. alveolar (pO2 of 13.3 kPa)
What is the typical O2 content of fully saturated blood of a healthy individual?
Each gram of Hb can combine with 1.34ml of O2
So, for a typical Hb of 150g/L, O2 content in fully saturated blood is 200ml/L (includes dissolved O2 too)
What is the approximate amount of O2 delivered to tissues?
Tissue PO2 typically 6kPa at rest when Hb is 65% saturated
Change in binding as moved from tissues to lungs (95% saturated) = 95 - 60 = 30% O2 given up by Hb at tissues
0.3 x 200ml/L (O2 content in full saturated blood) = 60ml O2 delivered per L of blood
Describe how venous blood haemoglobin keeps a oxygen reserve for when tissue demand increases.
Venous blood returns to heart after supplying tissues
In resting state, still has > 1/2 O2 bound
At tissues, Hb could possibly release more O2 if required for metabolism
So there is O2 reserve that can be mobilised if demand increases
What happens to the pO2 and therefore, the [O2] at the level of the tissues?
If tissue pO2 is lower, more O2 is given up by Hb as it diffuses down the increased gradient more quickly
Hb has less affinity for O2 as no. of molecules bound decreases however, there is a limit to how low tissue [O2] can drop before diffusion to cells is compromised
What tissues can tolerate a greater drop in pO2 and why?
Tissues with high capillary density can tolerate greater falls in pO2 e.g. heart muscle because diffusion occurs across shorter distance + higher SA allows maintenance of effective gradient between capillaries + cells
Why does the O2 dissociation curve shift?
Configuration of Hb depends on environment e.g. pH + temp so curve will shift along x-axis depending on whether the O2 affinity has increased or decreased
What factors shift the O2 dissociation curve to the right? Why?
Acidity
Increased temperature
Increased CO2
Increased 2,3-DPG/BPG
These factors decrease O2 affinity of Hb by stabilising tense form
Why would we want to shift the O2 dissociation curve to the right when there is high [2,3-DPG]?
2,3-DPG increases in RBCs in response to hypoxia so O2 is not bound due to low O2 affinity
What is the Bohr effect?
O2 dissociation curvw shifts along x-axis in response to acidic conditions; due to H+ ions + CO2 binding which both stabilise Hb’s tense form = at any given pO2, Hb binds less O2 as affinity has decreased -> O2 released more easily in tissues where pH is more acidic + CO2 in higher concentration - Hb releases up to 70% of bound O2
What is the Haldane effect?
Increasing O2 binding to Hb in lungs (pulmonary capillaries) reduces affinity for CO2 + H+ ions modifying Hbs structure -> more CO2 being offloaded at lungs (opposite of Bohr effect)
What is pH low in metabolising tissues?
Increased production of lactic acid + CO2 in tissues that are metabolically active + need O2 due to anaerobic metabolism
What is hypoxia? What can cause it?
Reduced availability of O2 to body tissues
Causes:
- Low blood volume
- Anaemia
- Low Hb
- Poor blood flow
- Pulmonary disease
In chronic hypoxia, the body will trigger various adaptive responses to attempt to increase O2 delivery to tissues. What are some examples of this?
Increased EPO = increased RBC production
Increased tissue capillary density
Increased 2,3-DPG/BPG levels
Increased ventilation
