3.3. Oxygen and carbon dioxide transport. Hemoglobin. Types of hypoxia. Flashcards
I. Transport of oxygen
1. What are the 2 forms of Transport of O2?
Transport of O2 occurs in 2 forms:
- Physically dissolved oxygen
- Oxygen saturation of hemoglobin
I. Transport of oxygen - Physically dissolved oxygen
2A. What is the O2-content of blood?
O2-content of blood:
- 0,03mL O2/L blood (1mmHg)
=> 3mL O2/L blood (if Pa = 100mmHg)
I. Transport of oxygen - Physically dissolved oxygen
2B. What is the O2-consumption of blood?
O2-consumption of body ~ 250mL O2/min
(- If we have 3mL O2/L dissolved in the blood, it means in order to supply the 250mL of
O2, what would be required is:
250 = 80 – 90 L blood/min (higher than CO) for O2-consumption of the body)
I. Transport of oxygen - Oxygen saturation for hemoglobin
3A. Characteristics of Oxygen saturation for hemoglobin
- Hemoglobin (Hb), found in RBCs, is a O2-binding protein
- Hb is a 4 subunit-protein (2α + 2β), that binds O2 with its heme groups
- 1moleofHbcanbind4molesofO2
I. Transport of oxygen - Oxygen saturation for hemoglobin
3B. What is the O2-binding capacity of Hb?
Hb: 2,3mmol/L
O2: 2,3mmol Hb * 4mmol O2 * 22,41mL O2/L blood (1mmol = 22,41 mL, that is why)
=> Hb can bind 206mL O2 in L blood
I. Transport of oxygen - IMPORTANT!
4. What is the amount of Hb-bound O2?
- Hb-bound: ~206mL O2/L (98% of O2 is in chemically Hb-bound form)
I. Transport of oxygen
5. What is the amount of O2 in physically dissolved form?
Physically dissolved: ~3mL O2/L (1,5% of O2 is in physically dissolved form)
=> Even though a small quantity, it is still important, because physically dissolved O2 determines the partial pressure of O2 in the lung and Hb-saturation depends on pO2
I. Transport of oxygen
6. When we have a gas transport of O2, what is the order of sequence?
1) O2 becomes physically dissolved in the plasma
2) Then diffuses into RBCs
3) Then binds to Hb
II. pO2 and percentage of Hb-saturation relationship
1. What is Saturation?
Saturation = how much fraction of total Hb has bound O2
- Hb binds 206mL of O2 in L/blood if it is 100% saturated with O2
- But depending on pO2, the saturation can be lower (since pO2 is lower)
II. pO2 and percentage of Hb-saturation relationship
2. Why is Hb-O2 binding cooperative?
- When 1 molecule binds to a single heme, the O2-affinity increases, allowing the 2nd
molecule to bind more easily - O2-affinity continuously increases as more O2 is incorporated into the heme, making it easier for the 3rd and 4th O2-molecule to bind even more easily
II. pO2 and percentage of Hb-saturation relationship
3. Describe O2 dissociation curve
- Sigmoid curve = when we have a curve with a steep initial part and a final plateau phase
- When binding is 0, the slope is relatively slow at the
start, because the affinity is slow - As O2 starts binding, the affinity increases
=> Causes a steep increase in the initial part of the curve - The O2-binding curve also has a plateau phase (at the final part), because if all Hb-molecules bind 4 O2- molecules, then Hb-O2-binding capacity is fully saturated
=> Hb cannot bind any more O2 = 100% saturation (maximum)
II. pO2 and percentage of Hb-saturation relationship
3A. What are pO2-levels in O2 dissociation curve (sigmoid)?
- In an average tissue, only 25% of O2 is used, which is available in the blood
- The remaining 75% works as a reservoir, which can be used during exercise or diseases
II. pO2 and percentage of Hb-saturation relationship
4A. What is the value for the saturation of Arterial blood?
97%
Saturation = how much fraction of total Hb has bound O2
II. pO2 and percentage of Hb-saturation relationship
4B. What is the value for the saturation of mixed venous blood?
75%
Saturation = how much fraction of total Hb has bound O2
III. Physiological factors that shift the O2 dissociation curve
1. What does it mean when we have right and left shifts in the O2 dissociation curve
1/ Right shift
-> affinity of Hb for O2 decreases
-> enhances O2
dissociation
- Left shift
-> affinity of Hb for O2 increases
-> inhibits O2 dissociation
III. Physiological factors that shift the O2 dissociation curve
2. What are the factors that shift the curve?
CO2, blood pH, temperature, concentration of 2,3 bisphosphoglycerate (2,3-BPG)
III. Physiological factors that shift the O2 dissociation curve
3. How can CO2 and pH shift the O2 dissociation curve
An increase in CO2-production results in the formation of protons (H+), which decreases the blood pH -> shifts the curve to the right
- CO2: CO2 + H2O (by carbonic anhydrase) ⇌ H2CO3 ⇌ H+ + HCO3-
=> Bohr effect: the effect of CO2 on the affinity of Hb for O2
1) H+ -> HHb (protonated Hb)
-> (lower O2-affinity) => RIGHT SHIFT
2) Carbamino-Hb(lower O2-affinity) => RIGHT SHIFT - H+↑ = pH↓: lower O2-affinity of Hb
III. Physiological factors that shift the O2 dissociation curve
4. How can Blood Temperature shift the O2 dissociation curve
An increase in temperature shifts the curve to the right
- Increasing temperature denatures the bond between O2 and Hb, which ↓ the concentration of oxyhemoglobin
- Increased temperature decreases O2-affinity
III. Physiological factors that shift the O2 dissociation curve
5. How can 2,3-bisphosphoglycerate (2,3-BPG) shift the O2 dissociation curve
- 2,3-BPG formed from 1,3-BPG (in Krebs cycle)
=> When pO2↓ (hypoxia)
-> Krebs cycle ↑
-> 1,3-BPG↑ -> 2,3-BPG↑ - So, 2,3-BPG is produced when there is hypoxia (exercise, high altitudes = pO2↓)
-> Low pO2-levels decreases the O2-affinity
-> curve shifts to right
III. Physiological factors that shift the O2 dissociation curve
6. How can the O2 dissociation curve shift to the right in case of exercise?
In the case of exercise, the O2 dissociation curve will always shift to right, because:
- Working muscle produces CO2, lactate
-> proton production↑, temperature increased due to ATP-production + energy consumption
III. Physiological factors that shift the O2 dissociation curve
7. How can the O2 dissociation curve shift to the Left in case of exercise?
The fetal Hb (HbF) has 2α and 2γ subunits, γ-subunit does not bind to 2,3-BPG
=> Left shifted, since there is a lack of 2,3-BPG
=> This process allows the fetus to take the O2 from maternal blood, because HbF
has higher O2-binding affinity than normal Hb
III. Physiological factors that shift the O2 dissociation curve
8. Is right shift physiologically useful?
YES!
- Right shift = less saturation
- Additional amount of O2 will be released into the tissue
-> right shift (produced by the mentioned factors), will improve the O2-delivery from blood to the tissue
-> the factors represent mechanism which are beneficial and helps the O2-supply of the tissues during exercise
III. Physiological factors that shift the O2 dissociation curve
9. Problems and solution arising from blood transfusion?
Blood taken from a donor and given to a recipient. During that time, blood must be stored.
- Problem: during the storing procedure, there will be metabolic processes -> 2,3-BPG↓
- Left shifted
- High O2-affinity = not good for recipient, because to give 75% O2, we have to go to
lower pO2-levels -> hypoxia in tissues - Solution: To prevent that, the 2,3-BPG levels must be maintained in the blood.
Glucose added and blood cooled down
-> cooling decreases the rate of BPG process and glucose supply metabolites to the citric acid cycle
III. Physiological factors that shift the O2 dissociation curve
10. Characteristics of CO
- Poison
- CO has 250x higher affinity to Hb than O2
- Hb 50% saturation of O2 occurs at 26mmHg, while
for CO it is 250x lower (~0,1mmHg)
=> If Hb saturated with CO, it cannot bind with O2 = PROBLEM
III. Physiological factors that shift the O2 dissociation curve
11. Explain this diagram
- CO: high affinity (250x) + increases O2-binding affinity of Hb (left shift)
- CO also has cooperativity (increases binding affinity for Hb) as O2 has to Hb
- Because of left shift, it requires much lower pO2 to release same amount of O2
IV. CO2 transport
1. What are the 3 ways of CO2 transport?
- Physically dissolved form
- Chemically bound form
- Bicarbonate form
IV. CO2 transport
2. How is CO2 transported in Physically dissolved form?
Physically dissolved form
- Solubility of CO2 in H2O is higher than O2 (about 20 times higher)
=> CO2 tension: 40mmHg -> 24mL/L blood (dissolved CO2 8x higher than O2)
=> Physically dissolved CO2 = 8 * 3mL/L blood = 24mL/L blood
IV. CO2 transport
3. How is CO2 transported in Carbamino form?
- Occurs in proteins (Hb), where amino groups react with CO2 and forms a carbamino group
- Carbamino form: 24mL/L blood
IV. CO2 transport
4. How is CO2 transported in bicarbonate form?
- In the blood plasma, CO2 reacts with H2O to form carbonic acid by an enzyme called carbonic anhydrase => bicarbonate
- H+ + HbO2 ⇌ HHb (protonated Hb) + O2
- Blood has buffers, and these can bind protons
- The most important buffer that can bind the proton, are the proteins -> Hb
IV. CO2 transport
4. How is CO2 transported in bicarbonate form?
- In the blood plasma, CO2 reacts with H2O to form carbonic acid by an enzyme called carbonic anhydrase => bicarbonate
- H+ + HbO2 ⇌ HHb (protonated Hb) + O2
- Blood has buffers, and these can bind protons
- The most important buffer that can bind the proton, are the proteins -> Hb
=> CO2 transported in bicarbonate form: ~432mL/L blood
IV. CO2 transport
5A. Explain the Cl- shift
In addition to the HCO3- formation, there is also a Cl- - shift in the RBC
- CO2 enters the RBC from tissues -> H2CO3 -> H+ + HCO3
- HCO3- accumulates in the RBC, by H+ binding to Hb
- Since there are a lot of Cl–HCO3- exchangers in the RBC
+) HCO3- will go to the plasma, and Cl- into the RBC
+) HCO3- ↑ in the plasma and Cl- ↑ in RBC
=> Not only the inside of RBC participates in the HCO3- - transport, but also the plasma - When there is an accumulation of HCO3- in RBC (which is exchanged for Cl-), we will have accumulation of extra osmotic particles as well
=> For that reason, the osmolarity in the RBC will increase: H2O-transport from plasma into the RBC
IV. CO2 transport
5B. How can appearance of HCO3- affect RBC?
Appearance of HCO3- affect the RBC a little bit
=> RBC slightly larger in venous blood (hematocrit)
IV. CO2 transport
5C. What is Bohr effect?
Bohr effect: the effect of CO2 on the affinity of Hb for O2
IV. CO2 transport
5C. What is Haldane effect?
Haldane effect: the effect of O2 on the affinity of Hb for CO2
V. Types of hypoxia
1. What is AVDO2 (arterio-jugular differences of oxygen)?
200mL – 150mL = 50mL O2/L blood
- AVDO2 = 50mL O2/L blood, so 1 liter of blood supplies an average of 50mL O2 to the tissues
V. Types of hypoxia
2. What are the values for Physically dissolved O2.?
- In arterial blood: 0,03mL O2/L blood/1mmHg * 95mmHg = ~3mL O2/L blood
- In venous blood: 0,03mL O2/L blood/1mmHg * 40mmHg = ~1,2mL O2/L blood
V. Types of hypoxia
3. The cause of hypoxia
Hypoxia occurs when, for some reason, the O2-delivery to tissues is insufficient
V. Types of hypoxia
4. What are the 4 types of hypoxia?
1) Hypoxic hypoxia: (low O2-levels)
2) Anemic hypoxia: (less functional Hb)
3) Circulatory (stagnant) hypoxia: (low perfusion (Q))
4) Histotoxic hypoxia: (tissue unable to use O2)
V. Types of hypoxia
5. What are the characteristics of Hypoxic hypoxia?
- Arterial pO2 is below normal, because alveolar pO2 is reduced (ex: due to high
altitudes, COPD) - under extreme conditions, AVDO2 is reduced
- when the capillary blood (O2-content between arterial + venous blood) has an
increase in non-oxygenated Hb = cyanosis
V. Types of hypoxia
6. What are the characteristics of Anemic hypoxia?
Anemic hypoxia: (less functional Hb)
- O2-carrying capacity of the blood has been reduced (ex: anemia, CO)
- For example, CO binds to Hb with such high affinity, that it prevents O2 from binding
V. Types of hypoxia
7. What are the characteristics of Circulatory (stagnant) hypoxia?
Circulatory (stagnant) hypoxia: (low perfusion (Q))
- Tissue is not receiving enough O2, because (1) heart cannot pump to tissue (2) arteries leading to tissues are blocked
V. Types of hypoxia
8. What are the characteristics of Histotoxic hypoxia?
Histotoxic hypoxia: (tissue unable to use O2)
- For example: cyanide poisons the systems that uses O2 to create energy and preventing them from using the O2
V. Types of hypoxia
9. Fills in the table
