Week 1- Carbon dioxide transport Flashcards
Where is CO2 produced and where does it need to be carried to?
How much CO2 is there in the blood compared to O2 and why?
How is it carried in the blood?
CO2 from the tissues needs to be carried to the lungs for excretion via gas exchange.
3x more CO2 in the blood than O2 as CO2 more soluble than O2.
Carried in solution/reacts chemically with water or carried in chemical combination.
What is the incremental CO2?
The difference between arterial and venous CO2 content is known as the incremental CO2. It represents the CO2 content picked up in tissues.
How is incremental CO2 picked up from the tissues carried in the blood? Reference percentages.
Incremental CO2 is carried in 3 forms:
1) Dissolved directly in plasma (either in blood plasma or inside RBC) = 10%
2) As carbaminocompound (where CO2 reacts with the NH2 amino group on proteins- importantly with haemoglobin inside RBC, but with other globulins in the blood plasma too). = 21%
3) As HCO3- ions= 69% (Again either remains in the blood plasma or inside RBC).
Describe the journey of CO2 from its site of production in the mitochondria to the blood.
What proportion of CO2 enters RBC when being carried back to the lungs vs the proportion remaining in plasma?
CO2 initially produced within the mitochondria, it diffuses out the cell into the extracellular space and across the endothelial cells of the capillary. Once across the capillary endothelium it enters the Plasma where it can remain or enter a RBC.
Most CO2 enters RBC to be carried in its three forms (89%), however 11% is carried within blood plasma (also in the three major forms : dissolved/carbaminocompound/HCO3-).
Define the following terms:
Acid
Base
Strong Acid
Weak acid
- Acid is a substance with donates a proton (H+).
- A base is a substance which will accept a proton (H+). (eg NaOH —> Na+ OH-) (OH + H+–> H2O)
- A strong acid is a substance which fully dissociates in water into its conjugate base and proton. eg) HCl —> H+ = Cl-
- A weak acid is a substance which only partially dissociates in water, reaching an equilibrium with its conjugate base that forms a buffer pair that can respond to changes in [H+] by reversibly binding H+. Eg) H2CO3 <=> H+ + HCO3-
Describe the normal partial pressures of O2 and CO2 in:
Venous blood
Alveolus
Arterial blood
- Venous blood: PvCO2= 6.5 kPa PvO2= 6.0 kPa
- Alveolus: PACO2= 5.3kPa PAO2= 13.3kPa
- Arterial blood: PaCO2= 5.3 kPa PaO2= 13.3 kPa
- Partial pressures of oxygen and carbon dioxide equilibrate with the arterial blood by the end of the pulmonary capillary (remember Hb should reach full saturation of O2 by 25% of the way along a pulmonary capillary).
Define pH
What is the normal pH range for the body? An average pH of the body?
pH = -Log 10 [H+]
pH is equal to the negative of log to the base 10 of the concentration of H+ ions in the solution. The concentration of H+ given in mol/L. This means for a 1 unit change in pH there is a ten fold change in [H+].
Normal pH range= 7.35-7.45
Average body pH = 7.4
What is the dissociation constant pK?
What is its equation?
what would this indicate in the context of an acid?
And in terms of buffering?
pK/ Dissociation constant is a constant that describes how easily a reaction will proceed to form its products, therefore how easily a substance will dissociate. Its value is given by the concentration of the products of a reaction over the concentration of the reactants.
Eg) HA –> H+ + A-
pK= [H+] + [A-] / [HA]
In context of an acid describes whether acid is a strong acid (forms lots of products- large pKa value) or a weak acid (only weakly dissociates, more reactant therefore smaller pKa value).
Can indicate extent of buffering in a solution of a particular pH.
What is the normal range for [H+] concentrations in the body?
- Normal range is 36-44 NANOMOLES/ L
- Remember pH = - log 10 [H+] where [H+] = MOL/L
Describe the different concentrations and types of acid produced within the body each day and the mechanism required to excrete this acid.
- Volatile acid: Body produces around 14,000 mmol/day of volatile H+ everyday from respiration in the tissues and the production of CO2. This travels within the circulation to the alveoli for excretion via the lungs.
- Non-volatile/ metabolic acid: Body produces 70mmol/day of non volatile acid i.e acid that is produced from metabolism that is not CO2, e.g sulphuric acid/ ketoacids/lactic acid. This acid is excreted via the kidneys which split H2CO3 into H+ ions for excretion and generate HCO3- that is reabsorbed.
Explain the relationship of CO2 and HCO3- in biological systems:
How does CO2 react in the blood plasma/inside RBC’s?
What is the equation for this reaction?
Why does this reaction not proceed to the right quickly in plasma?
How does this equation/ the relationship between CO2 and HCO3- determine pH?
- CO2 dissolves in plasma and RBC’s and reacts chemically with water to form carbonic acid (weak acid):
CO2 + H20 <=> H2CO3 <=> HCO3- + H+
- This reaction does not proceed to the right rapidly in plasma due to increased concentrations of HCO3- in the plasma. As only v small amounts of H2CO3 is produced it is normally omitted.
- The relationship between the concentration of CO2 (pCO2) in the blood and [HCO3-] ions determines the pH of the plasma:
- Increasing pCO2 increased concentration of CO2 dissolved in the blood, pushes the equation to the right to produce more [H+] and therefore decreases pH.
- Increasing HCO3- pushes eq. to left, decreasing the conc [H+], increasing pH.
What law determines the amount of CO2 dissolved in the blood?
State what this law says.
How does this law relate to O2 vs CO2 diffusion at the alveolar membrane?
How does this relate to transport of these gases in disease states?
Henry’s law determines the amount of CO2 dissolved in the blood.
Henry’s law: The amount of a gas dissolved in a certain volume of liquid at a certain constant temperature is directly proportional to the partial pressure of that gas.
Amount dissolved relies on: Partial pressure of that gas x solubility constant for that gas.
CO2 is 23x more soluble in water than O2. Means that at the alevolar- capillary membrane CO2 will diffuse much faster than oxygen. Normally no effect as the partial pressure of O2 is so much higher than CO2, however in disease states means O2 transport affected before CO2.
What is the Henderson Hasselbach Equation?
Henderson Hasselbach equation relates the pH of the blood plasma to ratio of the concentration of HC03 over the concentration of CO2 in the blood (which is determined by the partial pressure x solubility constant).
Remember the concentration of HCO3- is determined by the kidneys and the pCO2 determined by the lungs.
pH= pK + log10 [HCO3-]/ pCO2 x 0.23 (Kidneys/ lungs).
Where pK= 6.1 and is the dissociation constant for the reaction. Indicates the ratio of the concentrations of dissociated acid to undissociated weak acid. Buffering occurs best when the pK value is close to the pH.
0.23= solubility constant for C02
[HCO3-] = normally 25mmol/L
pCO2= 1.2 mM
pH= normally 7.4
When do buffer systems usually work their best?
- Buffer systems usually work their best at a pH close to their pK. (For the HC03/CO2 system pK 6.1, normal pH between 7.35-7.45).
What is physiological buffering?
What two systems form the physiological buffer and explain how changes in the concentrations of CO2/HCO3- would be regulated.
Physiological buffering decribes the defence and regulation of the body’s pH (normally 7.35-7.45) by regulating the concentration of [HCO3-] and pCO2 which is under the control of two different physiological systems.
The two systems involved are the respiratory system and the renal system.
Respiratory:
If there is more [H+] this will react with HCO3- to produce more CO2.
CO2 produced will be carried to the lungs for excretion which restores the pH.
Renal:
If there is more CO2 produced in respiring tissues this will react with water to produce more [H+] ions. This will be buffered by the generation of more HCO3- by the renal system.
Increased HCO3- will increase pH and restore it.
Describe the events after CO2 enters a RBC:
Focus on the role of CA
Describe the role of haemoglobin
Describe the chloride shift
- CO2 enters the RBC
- CO2 converted into HCO3- and H+ after combination with H20 by Carbonic Anhydrase.
- The H+ ions formed combined with haemoglobin via histidine residues on globin forming HHb.
- The HC03- produced increased the concentration within the cell, promoting its export via the Cl-/HCO3- anion exchanger
- Cl- enters the cell in exchange for HCO3- exported out- called the choride or hamburger shift.
- Means the majority CO2 is carried as HCO3- in the blood plasma (69%).
Describe two effects which promote oxygen delivery to tissues and carbon dioxide removal.
- As blood enters the systemic capillaries where tissues have a low partial pressure of oxygen and high partial pressure of carbon dioxide, oxygen is promoted to dissociate from haemoglobin by the Bohr effect:
- Increased pCO2, acidic pH promote conformational change in haemoglobin that promotes O2 dissociation.
Giving up O2 increases CO2 carriage in the blood - The Haldane effect:
- At any given pCO2 the total content of CO2 carried in the blood rises as pO2/Hb02 saturation falls.
- This promotes the removal of CO2 from systemic tissues and its transport back to the pulmonary capillaries.
Describe in detail how the Haldane effect promotes CO2 removal at the pulmonary capillaries
- Haldane effect describes the lowered affinity of haemoglobin for CO2 and H+ ions in the presence of oxygen.
- In the pulmonary capillaries there is a high partial pressure of oxygen and low partial pressure of CO2 which promotes O2 binding to Hb:
- Oxygen binding to haemoglobin alters the quaternary structure, which destabilises HHb and Carbaminohaemoglobin.
- Both of these effects promote CO2 loss by:
- Increase in free [H+] by dissociation from Hb when Hb combines with O2. This pushes the equation to the left (forming CO2 and H2O).
- Lowered HCO3- concentration by the reaction shifting to the left reverses the anion exchanger which now transports Cl- out and HCO3- in. This is then excreted as CO2.
- O2 binding destabilises carbaminohaemoglobin promoting dissociation of CO2.
Describe in detail how the Bohr effect promotes the delivery of oxygen to the systemic tissues
Bohr effect describes how the affinity of haemoglobin for oxygen declines in the presence of:
1) increased temperature
2) Increased pCO2
3) Acidic pH
4) 2,3 DPG - produced by glycolytic pathway under conditions of low o2.
Metabolically active tissues are warm, have high pCO2 and therefore lowered pH. These factors shift the equilibrium of haemoglobin in the relaxed state to the tensed state by altering the quaternary structure of Hb. This promotes O2 dissociation to the tissues.
Loss of O2 by Hb promotes CO2 uptake by the Haldane effect.
In venous blood how does the concentrations of HCO3 and pCO2 change?
What does this mean for pH change from arterial blood to venous blood?
- In venous blood the pCO2 increases from 5.3kPa in arterial to 6.1kPa.
- The concentration of HCO3- increases from 25mM in arterial to 27mM in venous.
- The increase in both pCO2 and HCO3- maintains the 20:1 ratio of HCO3: CO2 that needs to be maintained in order to regulate pH.
- pH drops from 7.4 in arterial to 7.38 in venous.
Describe carbon dioxide dissociation curves at different oxygen saturations of haemoglobin:
1) 70% saturation - venous blood
2) 100% saturation- arterial blood
What is important about the physiological range of co2 dissociation curves?
- Carbon dioxide dissociation curves are a plot of the partial pressure of carbon dioxide against the total CO2 content of the blood.
- Total CO2 content of the blood is formed by both CO2 reacting with H20 and being carried as HCO3- and by the formation of carbaminocompounds.
- As expected dissolved CO2 ( only 10%) increases with increasing pCO2.
- At oxygen saturation of 70% in venous blood, there is a larger proportion of total CO2 carried in the blood as haemoglobin is less saturated with oxygen meaning its conformation is more receptive to binding CO2 and H+ ions.
- At higher oxygen saturation of 97% as in arterial blood, there is proportionally less CO2 carried by the blood at each partial pressure of CO2 reflecting the low affinity of Hb-O for CO2/ H+ ions. (Haldane effect).
- At physiological range of pCO2 the dissociation curve is in the linear portion, meaning that CO2 binding does not saturate with increasing pCO2 at physiological range. More CO2 will be carried by the blood at increasing pCO2 with low oxygen.
- Physiological range pCO2: Arterial blood = 5.3 kPa Venous blood= 6.1 kPa.
What is a carbamino compound?
How does this relate to the Bohr effect?
- A carbaminocompound is formed when CO2 reacts with the NH2 groups of blood proteins (globulin in plasma) or hameoglobin in the RBC which forms carbaminoheamoglobin:
- CO2 + Protein-NH2 —> Protein-NH-COOH
- Relates to the Bohr effect as CO2 binding to haemoglobin forming carbaminohaemoglobin alters its conformation and lowers its affinity for oxygen promoting O2 dissociation.
