Respiratory Physiology L23

Question 1

What are the two ways blood transports oxygen?

Answer 1

1. Binds with haemoglobin
2. Dissolves in solution

Question 2

What is the carrying capacity of blood for oxygen?

Answer 2

• 200mls of oxygen per litre of blood
• 1g of haemoglobin can transport 1.39ml oxygen (aq) when fully saturted

Question 3

Structure of haemoglobin (Hb)

Answer 3

Dynamic molecule that moves and consists of polypeptide chains (amino acids linked together) forming a protein.
Hemoglobin has two main components: alpha and beta chains.
It has a spaghetti-like structure, with four distinct haem moieties (discs), each containing an iron ion (Fe2+).

Question 4

How do Haem moieties bind to oxygen molecules?

Answer 4

The binding of oxygen occurs in a cooperative manner, meaning the binding of the first oxygen molecule facilitates the binding of subsequent molecules.
The first oxygen molecule binds to a haem moiety that is accessible, while the other three are initially tucked inside the molecule.
When the first oxygen binds, the hemoglobin molecule undergoes an allosteric change (twisting), making it easier for the second oxygen to bind, and this process continues for the third and fourth oxygen molecules.
The entire process of oxygen binding happens rapidly, and the binding rate increases with each subsequent oxygen molecule due to the dynamic twisting of the hemoglobin.

Question 5

How is saturation measured?

Answer 5

Hemoglobin can carry a maximum of four oxygen molecules, and its saturation is measured by how many oxygen molecules are attached.
Fully saturated: 4 oxygen molecules attached.
Half saturated: 2 oxygen molecules attached (50% saturation).
The oxygen dissociation curve represents the percent saturation of hemoglobin against the partial pressure of oxygen.
Clinically, oxygen saturation is measured using a pulse oximeter.

Question 6

How to measure saturation?

Answer 6

Using a pulse oximeter

Question 7

What is a pulse oximeter?

Answer 7

Device that uses light to detect the colour of blood in the finger, which changes depending on the level of oxygenation.
Bright red indicates fully oxygenated blood (4 oxygen molecules bound to hemoglobin), while darker red indicates less oxygenation.
The device measures saturation based on the mass of hemoglobin molecules circulating in the blood.

Question 8

What is the partial pressure of oxygen?

Answer 8

Partial pressure of oxygen can be calculated as 21% of the barometric pressure, which gives approximately 160 mmHg at sea level.
At higher altitudes (e.g., Mount Everest), the barometric pressure decreases, leading to lower partial pressure of oxygen, making it harder to breathe (e.g., 53 mmHg on Everest).

Question 9

What is the barometric pressure?

Answer 9

Barometric pressure refers to the pressure caused by the weight of air above us, typically around 760 mmHg at sea level.
Barometric pressure is influenced by the weather, with lower pressure on wet days and higher pressure on clear days.
Barometers measure this pressure using mercury in a tube.

Question 10

What is the partial pressure of oxygen in the alveoli?

Answer 10

About 100mmHg, lower than atmospheric partial pressure due to dead space in the lungs and oxygen absorption by tissues in the airway.

Question 11

What are the gases in the atmosphere?

Answer 11

Nitrogen 78%
Oxygen 21%
Others 1 %

Question 12

Relationship between Oxygen saturation vs. partial pressure of oxygen

Answer 12

There is a sigmoidal (S-shaped) relationship between oxygen saturation of hemoglobin and the partial pressure of oxygen (PO2).
In systemic veins, the oxygen saturation is lower compared to the arteries.
At high PO2 (e.g., in the lungs), hemoglobin’s oxygen saturation is high, meaning hemoglobin has a high affinity for oxygen.
At low PO2 (e.g., in tissues around 40 mmHg), hemoglobin saturation is lower (~75%), meaning hemoglobin has a lower affinity for oxygen.

Question 13

Hemoglobin affinity for oxygen

Answer 13

Hemoglobin’s affinity for oxygen changes based on the partial pressure of oxygen.
In the lungs (high PO2), hemoglobin has a high affinity for oxygen, enabling efficient oxygen uptake.
In the tissues (low PO2), hemoglobin has a lower affinity for oxygen, encouraging oxygen to be released to the tissues.

Question 14

What does affinity mean again?

Answer 14

Affinity refers to the strength or tendency of a substance (like a molecule) to bind or interact with another substance. In the context of hemoglobin, affinity refers to how strongly hemoglobin binds to oxygen.

High affinity: Hemoglobin binds tightly to oxygen, making it less likely to release it. This occurs in places with high oxygen concentrations, like the lungs.
Low affinity: Hemoglobin binds loosely to oxygen, making it easier to release. This happens in areas with low oxygen concentrations, like tissues that need oxygen.

Question 15

What is the importance of hemoglobin’s changing affinity:

Answer 15

This changing affinity is crucial for physiological function. Hemoglobin needs to bind oxygen tightly in the lungs (where oxygen is plentiful) and release it in the tissues (where oxygen is needed).
The sigmoidal shape of the oxygen dissociation curve is partly due to the cooperative binding of oxygen to hemoglobin.

Question 16

What is cooperative binding?

Answer 16

Process where the binding of one molecule to a protein affects the binding of additional molecules. In the case of hemoglobin, cooperative binding means that the binding of the first oxygen molecule makes it easier for the next oxygen molecules to bind.

Here’s how it works with hemoglobin:

First Oxygen Binding: When the first oxygen molecule binds to one of the four haem moieties (the iron-containing parts) of hemoglobin, it is relatively difficult because the hemoglobin molecule is in a “tense” state.
Shape Change (Allosteric Effect): Once the first oxygen binds, hemoglobin undergoes a shape change (an allosteric effect), which increases its affinity for oxygen.
Subsequent Oxygen Binding: The shape change makes it easier for the second, third, and fourth oxygen molecules to bind. Each binding further increases the affinity for oxygen, making the process faster and more efficient.

Question 17

What is Oxygen unloading in tissues like?

Answer 17

In a healthy individual, hemoglobin is typically 99-100% saturated in the arteries.
In the tissues, hemoglobin releases about 25% of its oxygen, meaning the oxygen saturation in veins is about 75%.

Question 18

Affinities of O2 and PO2

Answer 18

Lower affinity at lower PO2 promotes oxygen release in tissues.
Higher affinity at higher PO2 promotes oxygen uptake in the lungs.

Question 19

Bohr Effect

Answer 19

How hemoglobin’s affinity for oxygen changes depending on the environment’s pH and the concentration of carbon dioxide (CO₂).

Hemoglobin’s affinity for oxygen:

Deoxyhemoglobin (Hb₄) binds to oxygen in stages, becoming progressively more saturated (e.g., Hb₄O₂ → Hb₄O₄ → Hb₄O₆ → Hb₄O₈), with fully saturated hemoglobin carrying 4 oxygen molecules (oxyhemoglobin).

CO₂ and pH interaction:
Carbon dioxide (CO₂) from tissues reacts with water (H₂O) in the presence of the enzyme carbonic anhydrase (found in red blood cells) to form carbonic acid (H₂CO₃).
Carbonic acid dissociates into H⁺ (protons) and bicarbonate ions (HCO₃⁻). The increase in H⁺ ions lowers the pH (making the environment more acidic).
Effect of pH on hemoglobin:

In acidic environments (like tissues with high CO₂), hemoglobin has lower affinity for oxygen. This causes oxygen to be released to the tissues.
In contrast, in the lungs, where there is less CO₂ and a higher pH (less acidic), hemoglobin has a higher affinity for oxygen, promoting oxygen uptake.

Question 20

Overview of shifting in the oxygen dissociation curve

Answer 20

Dissociation curves:

Three curves are depicted: one representing the lungs (left-shifted curve), one representing the tissues (right-shifted curve), and a middle curve representing a mean state.
The curves show percent saturation of oxygen in hemoglobin against the partial pressure of oxygen (PO₂).

Question 21

Overview of the 3 lines

Answer 21

Bohr Effect:

Describes how hemoglobin’s affinity for oxygen changes in different conditions.
Right shift (tissues): Hemoglobin has a lower affinity for oxygen at the tissues, aiding oxygen unloading.
This shift is caused by:
Increased CO₂.
Increased hydrogen ion concentration (lower pH).
Increased temperature (e.g., during exercise in skeletal muscles).
Increased diphosphoglycerate (DPG), a byproduct of aerobic metabolism, which binds to hemoglobin and promotes oxygen release.

Left shift (lungs): Hemoglobin has a higher affinity for oxygen in the lungs, aiding oxygen uptake.
Caused by:
Decreased CO₂ and hydrogen ion concentration.
Lower temperature (due to fresh air in the lungs).
Lower DPG levels (due to less metabolism in the lungs).
Physiological significance:

The Bohr shift ensures that hemoglobin readily picks up oxygen in the lungs (higher affinity) and releases it in the tissues (lower affinity).
For the same PO₂, hemoglobin’s affinity and oxygen saturation differ in the lungs and tissues, reflecting the body’s ability to efficiently manage oxygen transport.

Question 22

“For a given PO₂, more oxygen is given up at the tissues due to hemoglobin’s lower affinity for oxygen, which is essential for oxygen delivery to tissues.” meaning

Answer 22

In the lungs, hemoglobin’s affinity for oxygen is higher, ensuring adequate oxygen uptake.

Example from the curves:

At a PO₂ of around 30 mmHg, hemoglobin in the lungs has about 70% saturation.
At a similar PO₂ in the tissues, hemoglobin has significantly lower saturation, reflecting its lower affinity and promoting oxygen release.

Question 23

Overview of the oxygen dissociation curve - content

Answer 23

Oxygen saturation vs. content:

Oxygen saturation refers to the percentage of oxygen bound to hemoglobin, but content refers to the actual amount of oxygen in the blood.
In clinical settings, it is essential to measure both saturation and content.
Example: In anemia (a condition where there is a reduced amount of blood, hemoglobin, or red blood cells), the oxygen content is reduced due to less hemoglobin being present.
However, a pulse oximeter may still show high oxygen saturation since the remaining hemoglobin can still be fully saturated.
Clinicians must measure the oxygen content to understand the true oxygen-carrying capacity of a patient, especially in cases of blood loss or internal bleeding.

Anaemia Curve: Demonstrates the effect of a 50% reduction in hemoglobin (Hb) levels. The curve is shifted downward, showing that even though the partial pressure of oxygen (PO2) may remain the same, the overall oxygen content in the blood is reduced. This highlights the reduced oxygen-carrying capacity in cases of anemia.

Normal Curve: Represents the typical oxygen dissociation curve for a person with normal hemoglobin levels. The arterial blood (marked as “a”) shows near-maximum oxygen content, while the venous blood (marked as “v”) is lower, indicating oxygen delivery to tissues.

Anaemia Curve: Demonstrates the effect of a 50% reduction in hemoglobin (Hb) levels. The curve is shifted downward, showing that even though the partial pressure of oxygen (PO2) may remain the same, the overall oxygen content in the blood is reduced. This highlights the reduced oxygen-carrying capacity in cases of anemia.

P50: This point on the graph represents the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen. It is marked to show how changes in oxygen affinity can impact oxygen loading and unloading.

Question 24

CO2 transport in blood

Answer 24

CO2 is much more soluble in blood than oxygen (20 times more soluble).
CO2 is transported in the blood in three main forms:
Dissolved in solution.
As bicarbonate ions (the most important and primary form).
Bound to amine groups of proteins (including hemoglobin, forming carbamino compounds).

Question 25

What is Carbonic anhydrase?

Answer 25

Carbonic anhydrase is an essential enzyme in red blood cells that facilitates the conversion of CO2 to carbonic acid, which dissociates into bicarbonate and hydrogen ions.

Question 26

What reaction helps transport CO2 in blood?

Answer 26

CO2 + H2O forms carbonic acid, which dissociates into bicarbonate (HCO3-) and hydrogen ions (H+).

Question 27

What is carbaminohemoglobin?

Answer 27

Hemoglobin binds more CO2 than other plasma proteins due to its abundance in the blood.

Question 28

What are the importance of red blood cells?

Answer 28

Red blood cells concentrate both carbonic anhydrase (for CO2 transport) and hemoglobin (for oxygen transport), preventing blood from becoming too thick and viscous.

Question 29

What is the distribution of CO₂ in blood?

Answer 29

70% of CO₂ is transported in the plasma.
30% of CO₂ is transported in red blood cells (RBCs).

Question 30

What is bicarbonate formation?

Answer 30

The majority of CO₂ in plasma is in the form of bicarbonate (HCO₃⁻), which is rapidly formed in RBCs.
This formation is catalyzed by the enzyme carbonic anhydrase inside RBCs.
60% of the total CO₂ is carried as bicarbonate in the plasma, but this bicarbonate is initially formed in RBCs and diffuses into the plasma.

Question 31

Catalyzed vs. Non-Catalyzed Bicarbonate:

Answer 31

20% of bicarbonate in plasma is rapidly formed in RBCs, catalyzed by carbonic anhydrase.
5% of bicarbonate forms slowly in the plasma without the enzyme, as the process is much slower without carbonic anhydrase.

Question 32

Other Forms of CO₂:

Answer 32

A small percentage (around 5%) of CO₂ is bound to hemoglobin.
1% of CO₂ is bound to plasma proteins, while small amounts exist in solution or in the cytoplasm of RBCs.
Most CO₂ transport occurs through bicarbonate in the plasma, and this bicarbonate is predominantly formed in RBCs, thanks to the presence of carbonic anhydrase.

Question 33

CO₂ Transport in Tissues

Answer 33

CO₂ is produced in tissues and moves down its concentration gradient from tissues into the blood.
In the blood, CO₂ can dissolve directly in plasma or enter red blood cells (RBCs) (erythrocytes).
Within RBCs, the enzyme carbonic anhydrase facilitates the rapid conversion of CO₂ and water into bicarbonate (HCO₃⁻) and hydrogen ions (H⁺).
Most of the bicarbonate formed in RBCs diffuses into the plasma, creating a concentration gradient, leading to the chloride shift. Chloride (Cl⁻) enters RBCs to maintain electrical neutrality as bicarbonate leaves.
Protons (H⁺) produced in this reaction bind to hemoglobin, reducing its affinity for oxygen. This facilitates the release of oxygen into the tissues, completing the CO₂ transport mechanism.
Hemoglobin in an acidic environment (low pH) loses its oxygen-binding affinity, which helps oxygen to be released into tissues.
Some CO₂ also binds directly to hemoglobin, forming carbaminohemoglobin.

Question 34

CO₂ Transport in Lungs

Answer 34

In the lungs, the process reverses due to high oxygen (O₂) levels and low CO₂ levels.
Bicarbonate ions re-enter RBCs and are converted back into CO₂ via carbonic anhydrase. The resulting CO₂ then diffuses into the alveoli to be exhaled.
The chloride shift is also reversed, with chloride ions leaving RBCs as bicarbonate ions move in.
This reverse process ensures that CO₂ is expelled from the lungs efficiently.

Question 35

Eupnoea

Answer 35

Normal breathing

Question 36

Apnoea

Answer 36

No breathing

Question 37

Dyspnoea

Answer 37

Sensation of breathlessness

Question 38

Hypoxia

Answer 38

Low levels of oxygen

Question 39

Anoxia

Answer 39

No oxygen

Question 40

Asphyxia

Answer 40

Deprived of oxygen

Question 41

Hypercapnia

Answer 41

High carbon dioxide

Question 42

Hypocapnia

Answer 42

Low carbon dioxide

Question 43

Hyperventilate

Answer 43

Excessive breathing

Question 44

Hypoventilate

Answer 44

Shallow breathing (inadequate)

Question 45

Ischaemia

Answer 45

Inadequate blood supply to an organ

Question 46

Where are Peripheral Chemoreceptors located?

Answer 46

Located in the carotid bodies (at the bifurcation of the common carotid artery).

Question 47

Function of peripheral chemoreceptors

Answer 47

Sense blood gases like O₂ and CO₂ levels. Peripheral chemoreceptors respond to low O₂ (hypoxia) and high CO₂ or low pH.
Have the highest blood flow per unit volume, ensuring good access to circulating blood.
Responses are fast, typically within one breath, due to their direct access to blood gas levels.
Stimulated by hypoxia (low O₂), hypercapnia (high CO₂), acidosis (high H⁺), and increased sympathetic activity.

Question 48

Where are Central Chemoreceptors located?

Answer 48

Located in the brainstem, specifically= the medulla oblongata.

Question 49

Function of central chemoreceptors

Answer 49

Sensitive to CO₂ levels but not O₂. They indirectly sense CO₂ via the generation of protons (H⁺) in the cerebrospinal fluid.
CO₂ diffuses across the blood-brain barrier, where it is converted to H⁺, which stimulates central chemoreceptors.
Response to CO₂ changes is slower than peripheral chemoreceptors due to limited carbonic anhydrase in the cerebrospinal fluid.
Central chemoreceptors are critical in regulating breathing during sleep and maintaining steady CO₂ levels.

Question 50

Clinical Relevance

Answer 50

Central Hypoventilatory Syndrome (Ondine’s Curse)
Individuals born with few or no central chemoreceptors can experience life-threatening breathing problems, especially during sleep.
Central chemoreceptors play a crucial role in maintaining regular breathing, especially when CO₂ levels rise.

Question 51

Ventilatory response to hypoxia (only for peripheral chemoreceptors)

Answer 51

Eupnoea: This represents normal breathing at higher oxygen levels (PaO2 of around 100-150 mmHg).

Peak Ventilatory Response: As the oxygen levels (PaO2) drop, the ventilation rate increases to a peak. This is the body’s attempt to increase oxygen intake to compensate for low oxygen levels.

Depression: After the peak, further reductions in PaO2 cause a decrease in ventilation. This “depression” phase is likely due to a failure of the peripheral chemoreceptors or other factors in extreme hypoxia.

Apnoea/Gasping: At very low oxygen levels (PaO2 close to 0), ventilation is extremely low, leading to apnoea (cessation of breathing) or gasping, a final effort to take in oxygen.