3.3. Oxygen and carbon dioxide transport. Hemoglobin. Types of hypoxia. Flashcards

1
Q

I. Transport of oxygen
1. What are the 2 forms of Transport of O2?

A

Transport of O2 occurs in 2 forms:
- Physically dissolved oxygen
- Oxygen saturation of hemoglobin

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2
Q

I. Transport of oxygen - Physically dissolved oxygen
2A. What is the O2-content of blood?

A

O2-content of blood:
- 0,03mL O2/L blood (1mmHg)
=> 3mL O2/L blood (if Pa = 100mmHg)

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3
Q

I. Transport of oxygen - Physically dissolved oxygen
2B. What is the O2-consumption of blood?

A

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)

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4
Q

I. Transport of oxygen - Oxygen saturation for hemoglobin
3A. Characteristics of Oxygen saturation for hemoglobin

A
  • 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
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5
Q

I. Transport of oxygen - Oxygen saturation for hemoglobin
3B. What is the O2-binding capacity of Hb?

A

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

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6
Q

I. Transport of oxygen - IMPORTANT!
4. What is the amount of Hb-bound O2?

A
  • Hb-bound: ~206mL O2/L (98% of O2 is in chemically Hb-bound form)
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7
Q

I. Transport of oxygen
5. What is the amount of O2 in physically dissolved form?

A

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

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8
Q

I. Transport of oxygen
6. When we have a gas transport of O2, what is the order of sequence?

A

1) O2 becomes physically dissolved in the plasma
2) Then diffuses into RBCs
3) Then binds to Hb

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9
Q

II. pO2 and percentage of Hb-saturation relationship
1. What is Saturation?

A

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)

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10
Q

II. pO2 and percentage of Hb-saturation relationship
2. Why is Hb-O2 binding cooperative?

A
  • 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
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11
Q

II. pO2 and percentage of Hb-saturation relationship
3. Describe O2 dissociation curve

A
  • 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)
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12
Q

II. pO2 and percentage of Hb-saturation relationship
3A. What are pO2-levels in O2 dissociation curve (sigmoid)?

A
  • 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
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13
Q

II. pO2 and percentage of Hb-saturation relationship
4A. What is the value for the saturation of Arterial blood?

A

97%

Saturation = how much fraction of total Hb has bound O2

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14
Q

II. pO2 and percentage of Hb-saturation relationship
4B. What is the value for the saturation of mixed venous blood?

A

75%

Saturation = how much fraction of total Hb has bound O2

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15
Q

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

A

1/ Right shift
-> affinity of Hb for O2 decreases
-> enhances O2
dissociation

  1. Left shift
    -> affinity of Hb for O2 increases
    -> inhibits O2 dissociation
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16
Q

III. Physiological factors that shift the O2 dissociation curve
2. What are the factors that shift the curve?

A

CO2, blood pH, temperature, concentration of 2,3 bisphosphoglycerate (2,3-BPG)

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17
Q

III. Physiological factors that shift the O2 dissociation curve
3. How can CO2 and pH shift the O2 dissociation curve

A

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
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18
Q

III. Physiological factors that shift the O2 dissociation curve
4. How can Blood Temperature shift the O2 dissociation curve

A

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

19
Q

III. Physiological factors that shift the O2 dissociation curve
5. How can 2,3-bisphosphoglycerate (2,3-BPG) shift the O2 dissociation curve

A
  1. 2,3-BPG formed from 1,3-BPG (in Krebs cycle)
    => When pO2↓ (hypoxia)
    -> Krebs cycle ↑
    -> 1,3-BPG↑ -> 2,3-BPG↑
  2. 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
20
Q

III. Physiological factors that shift the O2 dissociation curve
6. How can the O2 dissociation curve shift to the right in case of exercise?

A

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
21
Q

III. Physiological factors that shift the O2 dissociation curve
7. How can the O2 dissociation curve shift to the Left in case of exercise?

A

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

22
Q

III. Physiological factors that shift the O2 dissociation curve
8. Is right shift physiologically useful?

A

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

23
Q

III. Physiological factors that shift the O2 dissociation curve
9. Problems and solution arising from blood transfusion?

A

Blood taken from a donor and given to a recipient. During that time, blood must be stored.

  1. 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
  2. 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
24
Q

III. Physiological factors that shift the O2 dissociation curve
10. Characteristics of CO

A
  • 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
25
Q

III. Physiological factors that shift the O2 dissociation curve
11. Explain this diagram

A
  • 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
26
Q

IV. CO2 transport
1. What are the 3 ways of CO2 transport?

A
  • Physically dissolved form
  • Chemically bound form
  • Bicarbonate form
27
Q

IV. CO2 transport
2. How is CO2 transported in Physically dissolved form?

A

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

28
Q

IV. CO2 transport
3. How is CO2 transported in Carbamino form?

A
  • Occurs in proteins (Hb), where amino groups react with CO2 and forms a carbamino group
  • Carbamino form: 24mL/L blood
29
Q

IV. CO2 transport
4. How is CO2 transported in bicarbonate form?

A
  • 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
30
Q

IV. CO2 transport
4. How is CO2 transported in bicarbonate form?

A
  • 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
31
Q

IV. CO2 transport
5A. Explain the Cl- shift

A

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
32
Q

IV. CO2 transport
5B. How can appearance of HCO3- affect RBC?

A

Appearance of HCO3- affect the RBC a little bit
=> RBC slightly larger in venous blood (hematocrit)

33
Q

IV. CO2 transport
5C. What is Bohr effect?

A

Bohr effect: the effect of CO2 on the affinity of Hb for O2

34
Q

IV. CO2 transport
5C. What is Haldane effect?

A

Haldane effect: the effect of O2 on the affinity of Hb for CO2

35
Q

V. Types of hypoxia
1. What is AVDO2 (arterio-jugular differences of oxygen)?

A

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

36
Q

V. Types of hypoxia
2. What are the values for Physically dissolved O2.?

A
  • 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
37
Q

V. Types of hypoxia
3. The cause of hypoxia

A

Hypoxia occurs when, for some reason, the O2-delivery to tissues is insufficient

38
Q

V. Types of hypoxia
4. What are the 4 types of hypoxia?

A

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)

39
Q

V. Types of hypoxia
5. What are the characteristics of Hypoxic hypoxia?

A
  • 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
40
Q

V. Types of hypoxia
6. What are the characteristics of Anemic hypoxia?

A

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

41
Q

V. Types of hypoxia
7. What are the characteristics of Circulatory (stagnant) hypoxia?

A

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

42
Q

V. Types of hypoxia
8. What are the characteristics of Histotoxic hypoxia?

A

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

43
Q

V. Types of hypoxia
9. Fills in the table

A