What must happen to co2 produced before being transported in other forms?
after produced by tissues? how are they transported? before lungs what happens?
Co2 produced by tissues has to first dissolve in plasma (PaCO2)
then the co2 is transported as HCO3- or bound to Hb
at lungs, CO2 will dissolve in plasma (PaCO2) before co2 exchange
co transport relative percentages
HCO3- = 70%
HbCO2 = 23%
Dissolved CO2 = 7%
How and why does transport of CO2 differ to O2?
why not haem?
what is the best transporter?
1) CO2 has a higher H2O solubility than O2 does – therefore a greater % of CO2 is transported simply dissolved in plasma (CO2 ≈ 7%, O2 ≈ 1%)
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛=𝑃𝑎𝑟𝑡𝑖𝑎𝑙 𝑝𝑟𝑒𝑠𝑠𝑢𝑟𝑒 ×𝑆𝑜𝑙𝑢𝑏𝑖𝑙𝑖𝑡𝑦
2) CO2 binds to Hb at different sites than O2 (R–NH2 residues at the end of peptide chains, forming carbamino-Hb, R-NHCOOH) and with decreased affinity. Thus, a lower % of CO2 is transported in this manner (≈ 23%).
3) CO2 reacts with water to form carbonic acid, which accounts for the majority (≈70%) of CO2 transported.
CO2 + H2O (eqilibirum) H2CO3 (equilibrium) H+ + HCO3-
Venous blood carries more CO2 than arterial blood (‘The Haldane effect’). Why?
Venous blood has more deoxy haem compared to oxyhaem
Deoxy-Hb has a higher affinity for CO2 and H+ than oxy-Hb does.
∴ ↑oxy-Hb = ↓CO2 carried (so arterial blood carries less)
Haldane effect + COPD patient
consequence of starting o2 therapy quickly in patients with severe COPD?
what is CO2 and O2 like in COPD patients? what happens when you increase O2 level quickly? what will a healthy individual do in this scenario and why is this not possible with a copd patient?
One consequence of the Haldane effect is that it can be dangerous to start supplemental O2 therapy too quickly in patients with severe COPD as sudden oxygenation of their blood can cause a rapid accumulation of CO2.
COPD patients chronically hypoventilate their lungs, therefore CO2 levels rise within the body. However the blood of such patients has greater CO2 capacity due to the low levels of O2 and the Haldane effect (these patients are both hypercapnic and hypoxaemic). When oxygen levels suddenly increase (e.g. with the onset of supplemental O2 therapy), the CO2 is displaced from the blood as it can carry less CO2 bound to Hb and as HCO3-. This leads to sudden very high levels of CO2 within the body, potentially leading to a dangerous acidaemia.
Whilst a healthy individual would simply increase their level of ventilation to get rid of the excess CO2, this is not possible in the COPD patient due to the hypoventilation and deterioration in lung function associated with the disease.
Haldane effect in the presence of o2 - long
what happens to hb when o2 binds?
what effect does H+ binding on Hb have?
When O2 binds Hb, a conformational change is induced to the structure of Hb which reduces the affinity of Hb for both CO2 and H+ (which results in oxygenated Hb carrying less CO2 and H+).
The degree of H+ binding to Hb has a further knock on effect on CO2 transport. Hb-H+ binding effectively acts as a buffer and removes H+ from the surrounding environment. This in turn shifts the equilibrium of the reaction: CO2 + H2O = H2CO3 = H+ + HCO-3, to the right.
Due to Le Chatelier’s principle, the removal of product induces more substrate to react until the previous equilibrium - the relative proportion of substrate vs. products - is re-established. The net effect is that dissolved CO2 is pulled out of the plasma and into storage as bicarbonate. This CO2 lost via conversion to HCO3 is then replaced by fresh CO2 produced by tissues and thus the overall amount of CO2 carried within the blood increases. Conversely, where oxygenation of blood increases, Hb-H+ binding is reduced and the reverse effect occurs, decreasing CO2 carrying capacity:
Haldane effect in the presence of o2 - short
what effect does presence of o2 have on affinity of haemoglobin to co2/H+?
in the presence of o2, the affinity of haemoglobin for co2/H+ will decrease,
therefore at any give partial pressure, the amount of binding will go down hence any given amount of co2/H= will go down but has to go somewhere so shifted backwards in the pathway therefore co2 kicked out of rbc and any co2 in rbc will be pushed into the plasma
overall less co2 present in blood if o2 is present which is a good thing in the lungs as more co2 will be lost from blood into the alveoli to be expelled
Haldane + bohr effect
what are their effects?
Haldane effect - o2 effect on co2
Bohr effect - co2 effect on o2
Haldane effect in tissues
where does co2 come from and what happens after that?
what enables further co2 movement? enzyme involved?
what is rbc impermeable to?
role of deoxy-hb in this?
how is electrial neutrality maintained?
1) CO2 is produced by respiring cells and dissolves in the plasma + enters RBCs.
2) Conversion of CO2 + H2O to H2CO3 within RBCs (catalysed by carbonic anhydrase)
3) The effective removal of CO2 by (2) enables further CO2 to diffuse into the RBC (& more can then enter the plasma).
4) H2CO3 ionises to HCO3- + H+. The RBC cell membrane is impermeable to H+, therefore H+ cannot leave
5) Accumulation of H+ within cell, and ∴ cessation of (2), is prevented by deoxy-Hb acting as a buffer and binding H+. Movement of O2 into tissues from RBCs ∴ ↑[deoxy-Hb] and enables more CO2 to be transported.
6) The increased [HCO3-] creates a diffusion gradient for HCO3- to leave the cell. It is exchanged for Cl- to maintain electrical neutrality.
Haldane effect in Lungs
why does co2 diffuse out of blood into airspace?
what increase free H+? effect of this?
what binds to H+ and how?
1) Low PACO2, creates a diffusion gradient for CO2 to diffuse out of the blood into the airspace
2) Increased PAO2 leads to O2-Hb binding. O2-Hb binds less H+ than deoxy-Hb, increasing free [H+]
3) Increased free [H+] leads to increased H2CO3 and ultimately CO2 which contributes to CO2 plasma saturation.
4) The changing equilibrium of carbonic acid reaction, also leads to decreased [HCO3-], as it binds the free H+. This creates a diffusion gradient that allows HCO3- ions to entry the RBC in exchange for Cl-.
Co2 and Ph affect o2-Hb affinity
effect of co2 on o2-hb affinity?
how does co2 do this? ( 2 ways, direct and indirect)
Increased CO2 levels decrease O2-haemoglobin binding affinity and decrease the amount of O2 bound to Hb at a given PO2.
The level of CO2 present mediates this effect both directly and via its relationship with blood pH following conversion to carbonic acid (i.e. more CO2 = more H+ = lower pH = decreased O2-Hb affinity = less O2 carried).
This is because when CO2 and H+ bind to the Hb molecule (at different sites to O2), they induce a conformation change in the Hb molecule which changes the structure of the O2 binding site, altering O2-Hb binding affinity.
The role of the bicarbonate buffering system in maintaining blood pH
how can chnages in pH be resisted?
how does co2 effect pH? how is this related to the resp system?
The reaction of CO2 with H2O to form H+ and HCO3- (via H2CO3) can proceed in both directions depending on the relative quantities of each molecule and the conditions present. Therefore changes in pH (the -log10 form of H+ concentration) are resisted by converting excess H+ to H2O and CO2.
The excess CO2 can then be removed at the lung by increasing ventilation. Conversely, where pH increases, ventilation can be reduced to increase PaCO2 and yield more H+. Therefore the respiratory system has a key role in maintaining blood pH
accumulation of co2 (hypoventilation) -> increased H2CO3 -> increased H+ (acidosis)
removal of co2 (hyperventilation) -> decreased H2CO3 -> decreased H+ (alkalosis)
The lungs & kidneys maintain blood pH homeostasis by regulating PaCO2 & [HCO3-], respectively
what does kidmey regulate? time?
what does lungs regulate? time?
Renal regulation of HCO3-
E.g. regulating reabsorption/ excretion in glomerular filtrate (timeframe = hours to days)
Respiratory regulation of PaCO2
E.g. regulating ventilation (timeframe = minutes)
ph = log (hco3-)/paco2
Blood ph and ratio of HCO3- and PaCO2
increase and decrease of both, how does it effect pH?
This means that blood pH is determined by the ratio of HCO3- to PaCO2, and that changes in either will result in disruptions in pH:
↑ PaCO2 = ↓ pH (unless [HCO3-] changes proportionally, in the opposite direction)
↓ PaCO2 = ↑ pH (unless [HCO3-] changes proportionally, in the opposite direction)
↑ [HCO3-] = ↑ pH (unless PaCO2 changes proportionally, in the opposite direction)
↓ [HCO3-] = ↓ pH (unless PaCO2 changes proportionally, in the opposite direction)