D.6 Transport of respiratory gases Flashcards
1
Q
Define gaseous exchange
A
The diffusion of gases between the alveoli and capillaries in the lungs.
2
Q
What is the main purpose of the alveoli?
A
Gas exchange
3
Q
The cells forming the alveolus are called ___
A
Pneumocytes
4
Q
What are the two types of pneumocytes?
A
Type I and type II
5
Q
Describe the structure and function of type I pneumocytes
A
- They are flat with a great surface area (approximately 90–95% of the alveolar surface).
- They are involved in the process of gas exchange between the alveoli and blood.
6
Q
Describe the structure and function of type II pneumocytes
A
- They have a cubic shape and cover a small fraction of the alveolar surface area (5%).
- They secrete pulmonary surfactant, a fluid that decreases the surface tension within the alveoli.
- They are also capable of cellular division, giving rise to more type I pneumocytes when the lung tissue is damaged.
7
Q
Diagram and micrograph of the structure of the alveolus (images to the left), light micrograph of lung ×100 (top right) and ×400 (bottom right)
A
8
Q
Identifying structures in an alveolus for the exam
A
You should be able to identify pneumocytes, capillary endothelium cells and blood cells in light micrographs and electronmicrographs of lung tissue.
9
Q
What does the rate of gaseous exchange depend on?
A
The pH of blood
10
Q
Explain how the rate of gaseous exchange depends on the pH of the blood
A
- It is regulated to stay within the narrow range of 7.35 to 7.45. Within blood plasma and tissue fluids, hydrogen carbonate, proteins, and ions (such as phosphate) act as buffers to maintain the pH close to neutral (slightly alkaline).
- Carbon dioxide combines with water, producing carbonic acid that lowers the pH.
- The carbonic acid dissociates into alkaline hydrogen carbonate, increasing the pH, plus a hydrogen ion that acidifies the medium, decreasing the pH.
- This is called the hydrogen carbonate buffering system
11
Q
Equation for the hydrogen carbonate buffering system
A
12
Q
What is the range that the pH of blood is regulated to stay within?
A
7.35 to 7.45
13
Q
What is a difference between Type I and Type II pneumocytes?
A
Type I have a larger surface area than Type II pneumocytes (to allow for gaseous exchange between the alveoli and blood).
14
Q
How does the hydrogencarbonate buffering system maintain the pH of blood within limits?
A
Dissolved carbonic acid dissociates into hydrogen carbonate and hydrogen ions.
15
Q
What is hemoglobin and what is it made up of?
A
- Haemoglobin is a protein composed of four peptide chains, two alpha and two beta chains, each with a ring-like heme group containing an iron atom.
- Oxygen binds reversibly to these iron atoms.
16
Q
Describe the structure of adult hemoglobin
A
This structure is oxyhaemoglobin, with four oxygen molecules.
17
Q
Diagram of a molecule of adult oxyhemoglobin
A
18
Q
Describe the transport of respiratory gases between the mother and fetus during pregnancy
A
- During pregnancy, the mother must deliver O2 to the fetus and remove CO2 through the placenta.
- Mother and fetal blood never mix, so capillaries from both must come in close proximity for exchange to happen.
19
Q
Describe the structure of fetal hemoglobin and the reason for it
A
- In order to get O2 into fetal blood, the hemoglobin in fetuses is slightly different from the adult hemoglobin.
- Instead of having two alpha and two beta peptides, the fetal hemoglobin has two alpha and two gamma peptides.
20
Q
Diagram of fetal deoxyhemoglobin
A
21
Q
Fetal hemoglobin has more ___ than adult haemoglobin.
A
Affinity for oxygen
22
Q
Picture of the protein sequence alignment obtained using pBLAST for the gamma peptide of fetal haemoglobin and beta peptide of adult haemoglobin
A
23
Q
Describe the pBLAST for fetal (Query 1) and adult hemoglobin (Sbjct 1)
A
- As you can see in this sequence alignment, there are some similarities between the sequences of beta and gamma hemoglobin peptides, but there are also some amino acids that are different.
- This allows fetal haemoglobin to bind O2 with a greater affinity, therefore extracting it from the mother’s blood.
24
Q
What is myoglobin?
A
The protein used to bind oxygen in muscles.
25
Describe the structure and function of myoglobin
- It consists of only one peptide chain and a heme group containing iron.
- There is no sequence similarity in haemoglobin and myoglobin chains.
- Myoglobin can only bind one oxygen molecule, but this binding is stronger than that in haemoglobin.
- Therefore myoglobin can take the oxygen from haemoglobin in respiring muscle cells.
26
Diagram of myoglobin
27
In what way are hemoglobin and myoglobin the same?
They are oxygen binding proteins as both contain iron molecules.
28
In what way is fetal haemoglobin different to adult haemoglobin?
It has a greater affinity for oxygen.
In order to get O2 into fetal blood, the haemoglobin in fetuses is slightly different to the adult haemoglobin, making it take in oxygen more readily.
29
How is oxygen transported in humans?
Oxygen is transported mainly bound to haemoglobin as oxyhemoglobin (98.5%) and dissolved in plasma (1.5%).
30
Explain how oxygen is bound to hemoglobin
- Oxygen is bound to haemoglobin in the lungs.
- Once the first heme binds to oxygen, there is a small change in the protein structure of haemoglobin, making the heme of another chain join oxygen more easily.
- Cooperative oxygen binding by haemoglobin causes conformational changes in an individual peptide that are propagated to the other peptides.
- The joining of the third and fourth oxygen molecules becomes easier due to this allosteric change in the haemoglobin molecule, leading to an S-shape or sigmoid curve.
31
How does oxygen binding to hemoglobin change in the different tissues of the body?
- Oxygen remains tightly bound to hemoglobin in the lungs, but it will be progressively released as partial oxygen pressure drops in the different tissues of the body.
- The release of a second, and even more so the third oxygen molecule, require smaller drops in pressure.
32
What does the oxygen dissociation curve show?
How the partial pressure of oxygen (pO2) in the tissues determines the percentage of haemoglobin that contains oxygen at pH 7.4 and 38°C.
33
Diagram of the oxygen dissociation curve for adult haemoglobin
34
Define partial pressure
The individual pressure exerted independently by a particular gas within a mixture of gases.
35
How is blood pumped throughout the body?
- The pulmonary vein brings oxygenated blood to the left side of the heart, which pumps it via the aorta to all parts of the body.
- When this blood returns to the right side of the heart, it is pumped along the pulmonary artery.
36
Blood cells in the capillaries surrounding the alveoli carry ___
100% of the hemoglobin as oxyhemoglobin (with four molecules of oxygen bound).
37
Where do the capillaries surrounding the alveoli lead to?
The pulmonary vein, which carries blood to the heart.
38
What happens as the blood leaves the heart?
- The partial pressure of oxygen decreases (to about 40 mmHg in the pulmonary arteries) and the hemoglobin molecule releases one oxygen molecule.
- This causes an allosteric change in the hemoglobin molecule that makes the further release of the other oxygen molecules easier, as less energy is required.
- This means that a smaller drop in partial pressure is required to liberate a molecule of oxygen, leading to an S-shape or sigmoid curve.
- In this way, hemoglobin attaches the largest possible amount of oxygen in the lungs and delivers all of it where and when it is needed.
39
Fetal hemoglobin- oxygen dissasociation curve (check/reword)
- Fetal haemoglobin binds O2 with a greater affinity, therefore extracting it from the mother’s blood in the placenta.
- This means that at lower partial pressures of O2, the fetal hemoglobin loads O2 easier than adult hemoglobin.
- This would cause a shift to the left in the oxygen dissociation curve.
40
Affinity for oxygen in myoglobin vs. hemoglobin
- Myoglobin has a stronger affinity for oxygen than haemoglobin.
- Because myoglobin is formed by only one peptide, there is no allosteric effect in the molecule.
41
Graph showing the oxygen dissociation curves for myoglobin and fetal and adult hemoglobin
42
What is the oxygen partial pressure in tissues?
10 to 40 mmHg.
The oxygen partial pressure in pulmonary arteries is around 40 mmHg, therefore in the tissues, it is lower than this.
43
What determines the difference in shape of the haemoglobin and myoglobin dissociation curves?
The cooperative effect of four heme groups in hemoglobin.
44
What happens when carbon dioxide diffuses into the blood in the respiring tissues?
- It dissolves in plasma.
- A small amount remains dissolved in plasma (around 5-10%), while most diffuse into red blood cells.
45
What can hemoglobin carry besides oxygen?
- Besides oxygen, hemoglobin can carry other molecules such as carbon dioxide.
- Around 20-25% of the carbon dioxide in the red blood cells binds to hemoglobin, forming carbaminohaemoglobin (HbCO2).
46
Explain how carbon dioxide is transformed in red blood cells into hydrogen carbonate ions
- When CO2 enters the erythrocyte, it combines with water to form carbonic acid (reaction catalyzed by carbonic anhydrase)
- The carbonic acid (H2CO3) then dissociates to form hydrogen ions (H+) and bicarbonate (HCO3–)
- Bicarbonate is pumped out of the cell in exchange with chloride ions (exchange ensures the erythrocyte remains uncharged)
- The bicarbonate in the blood plasma combines with sodium to form sodium bicarbonate (NaHCO3), which travels to the lungs
- The hydrogen ions within the erythrocyte make the environment less alkaline, causing hemoglobin to release its oxygen
- The hemoglobin absorbs the H+ ions and acts as a buffer to maintain the intracellular pH
- When the red blood cell reaches the lungs, bicarbonate is pumped back into the cell and the entire process is reversed
47
What is the chloride shift? (continuing from prev flashcard)
- The H+ joins the hemoglobin molecule to form a weak acid called hemoglobin acid (HbH).
- The bicarbonate (hydrogen carbonate) leaves the red blood cells to enter the blood plasma.
- To balance the electric charge in the red blood cells, chloride ions (Cl-) enter the cells by diffusion.
- This is called the chloride shift.
48
Where does the opposite of the chloride shift occur?
In pulmonary capillaries, where the decrease in intracellular HCO3- induces the outward movement of Cl-.
49
Diagram showing the transport of O2 and CO2 in blood
50
What is the difference between how carbon dioxide and carbon monoxide join hemoglobin?
Carbon dioxide joins haemoglobin reversibly, while carbon monoxide does this irreversibly, forming stable complexes that cannot be removed, rendering the hemoglobin useless, making it very toxic.
51
What is formed when carbonic acid is catabolysed by carbonic anhydrase?
Carbon dioxide and water.
Water joins carbon dioxide and is converted to carbonic acid (H2CO3) by the enzyme carbonic anhydrase. This reaction is reversible, so it goes back to carbon dioxide and water by the same enzyme.
52
What did Christian Bohr discover and where?
In 1904, Christian Bohr discovered that the affinity of haemoglobin for oxygen is related to the pH of blood and to the partial pressure (or concentration) of CO2 (pCO2).
53
Explain what Bohr discovered
- The affinity of hemoglobin for oxygen is related to the pH of the blood and to the partial pressure (or concentration) of CO2 (pCO2).
- An increase in blood acidity causes a shift of the oxygen dissociation curve to the right, and a decrease in acidity (a more alkaline pH) will cause a shift to the left.
54
Diagram of the Bohr shift at 37ºC and (a) different pH values and a fixed pCO2 of 40 mmHg (b) different CO2 partial pressures and a fixed pH of 7.24.
55
Analyzing Bohr shift curves for the exam
You should analyse different curves in different conditions.
56
Bohr shift (https://www.youtube.com/watch?v=wgSUdxrlO8Y)
-The oxyhaemoglobin dissociation curve demonstrates the saturation of haemoglobin by oxygen under normal conditions
-pH changes alter the affinity of haemoglobin for oxygen and hence alters the uptake and release of O2 by haemoglobin
-Carbon dioxide lowers the pH of the blood (by forming carbonic acid), which causes haemoglobin to release its oxygen
-This is known as the Bohr effect – a decrease in pH shifts the oxygen dissociation curve to the right
-Cells with increased metabolism (i.e. respiring tissues) release greater amounts of carbon dioxide (product of cell respiration)
-Hence haemoglobin is promoted to release its oxygen at the regions of greatest need (oxygen is an input of cell respiration)
57
What is the Bohr effect?
The shift of the oxygen dissociation curve to the right with the increase of H+ or CO2, as the oxygen binding affinity is inversely related to acidity and carbon dioxide concentration.
58
What does a shift to the right in the sigmoid dissociation curve mean?
A decreased O2 affinity, therefore O2 is released.
59
What causes the oxygen dissociation curve to shift to the right?
Increase in acidity or in CO2.
If the pH of the blood is more acid, there will be a greater availability of H+. The H+ combines with haemoglobin, causing oxyhaemoglobin dissociation and the liberation of O2. The larger the amount of CO2, the greater the amount of H+ produced. This will allow the greater liberation of oxygen in respiring tissues.
60
How does the CO2 concentration of blood affect the release of O2 in tissues?
More CO2 in blood will cause a greater release of O2.
The larger the amount of CO2, the greater the amount of H+ produced. The H+ combines with the haemoglobin, thus O2 is released by haemoglobin to the tissues.
61
What does the rate at which oxygen is consumed when cell respiration takes place vary with?
The general state of activity of the body.
62
How may vigorous exercise change the body's need for oxygen?
- It may increase the demands of the tissues for oxygen by 20 to 25 times.
- This increased demand is met by increasing the rate and depth of breathing.
63
What part of the body controls the rate of ventilation in response to changes in pH and how?
The respiratory control center in the medulla oblongata controls the rate of ventilation in response to changes in pH by sending impulses to the external intercostal muscles and diaphragm.
64
How are levels of CO2 in the blood detected by the body?
- In the aorta and the carotid artery (in the neck), there are special chemoreceptors that detect the levels of carbon dioxide in the blood.
- Additionally, the carotid receptors detect changes in the pH of the blood.
65
What happens to the ventilation rate during exercise?
It increases in response to the amount of CO2 in the blood.
66
The ___ group is in charge of inspiration and the ___ group of expiration.
Dorsal
Ventral
67
It is the ___ that interacts with those in the ___ to make the rhythm smooth.
Center in the pons
Medulla
68
What is total lung capacity?
The maximum volume of air in lungs (6 dm3).
69
What is residual volume?
The volume of air that remains in the lungs (1.5 dm3).
70
What is tidal volume?
The volume of air breathed in and out in normal breathing (0.5 dm3).
71
How can ventilation rate be measured?
- Using a spirometer.
- Patients blow as fast and hard as possible into a tube attached to a kymograph that measures the volume and speed of air blown out.
- During exercise inspirations and expirations are deeper and more frequent.
72
Diagram of a spirometer and ventilation rate
73
What is residual air?
Air that remains in the lungs.
74
How does exercise affect breathing rate?
More frequent and deeper inspirations.
75
What effect does altitude have on the air you breathe in?
- Although the percentage of oxygen in inspired air is constant at different altitudes, the fall in atmospheric pressure at higher altitude decreases the partial pressure of oxygen (pO2).
- As pO2 decreases, the percentage saturation of haemoglobin decreases rapidly.
- Hemoglobin has low affinity for oxygen at low pO2, so it is not fully saturated as it passes through the lungs.
- This means that the tissues of the body are supplied with less oxygen.
76
Graph showing the partial pressure of oxygen at sea level (0m) and at high altitude (5800m)
77
What is mountain sickness and what are its symptoms?
- This may occur when a person travels from low to high altitude.
- The most common symptoms are headache, nausea and dizziness.
- High blood pressure in mountain sickness leads to body fluid buildup.
- After several days (or even weeks), the body becomes acclimatised.
78
What changes does acclimatization include?
- Heart pumps faster.
- Blood vessels increase in diameter.
- Lung ventilation rate increases.
- Muscles produce more myoglobin to store more oxygen.
- More capillaries develop in the alveoli.
- The number of erythrocytes increases.
79
Why are there more erythrocytes in the blood during acclimatisation?
- Bcause there is an increased production of the hormone erythropoietin (EPO).
- This peptide hormone is produced in the kidneys and acts in the bone marrow, on precursors of erythrocyte production.
- EPO levels in blood are usually low, around 10 mU/ml of blood, but can increase to 10,000 mU/ml in cases of lack of oxygen.
80
What does the greater amount of EPO during acclimation lead to?
- It will increase the number of erythrocytes.
- This means that more oxygen is delivered to the muscles, therefore improving endurance capacity.
81
How is EPO used in sports?
- EPO has been used in sports as a form of doping.
- In addition to ethical implications, the increase in EPO produces dangerous negative effects, due to excess number of erythrocytes.
82
What are the negative effects that the increase in EPO can cause?
- Increased blood viscosity.
- Reduced blood flow.
- High blood pressure.
- Increased risk of coronary heart disease.
83
Prohibition of EPO
Its use has been prohibited by most sports organizations, and EPO is now being tested for as part of the Olympics anti-doping program.
84
Describe high-altitude training
- Athletes may take advantage of altitude acclimatisation to increase their performance.
- This could give them a competitive advantage; however, it can also increase complications related to altitude sickness.
85
Advantages of high altitude training
- Increased stamina.
- Increased sprint speed.
- Natural increase in EPO.
- Increase in erythrocytes.
- Increased haematocrit (% red blood cells in blood).
- Increase in haemoglobin concentration.
- More oxygen to muscles.
- Increased mitochondria in muscle cells.
- More myoglobin in muscles.
- Larger lungs.
- More capillaries in lungs and muscles.
- Increase in ventilation rate.
- Increase in cardiac output/heart rate.
- More gaseous exchange.
- Negative to anti-doping.
86
Disadvantages of high altitude training
- Altitude sickness: nausea, headache.
- Increased blood viscosity.
- High blood pressure.
- Body fluid build-up.
- Larger heart.
- Increased risk of stroke.
- Increased risk of venous thrombus.
- Lowered immunological response.
- Unfair advantage.
87
What chemicals do cigarettes contain?
Tar, nicotine, tobacco and other chemicals.
88
What is produced during smoking?
Carbon monoxide
89
How does smoking affect lung function?
- Carbon monoxide binds irreversibly to haemoglobin; therefore gaseous exchange is diminished, causing the smoker to get breathless when exercising.
- Tar coats lining of alveoli, increasing the risk of emphysema.
- Breathing infections are common due to the fact that cilia do not move mucus out of airways.
- Cough due to irritation of bronchi and bronchioles.
- Chronic bronchitis.
90
What other health problems can come from smoking (other than bronchitis)?
- Increased chances of developing lung, throat or mouth cancer.
- Cardiovascular disease due to atherosclerosis.
- Nicotine increases heart rate and blood pressure.
- Nicotine makes blood platelets stickier, increasing the chance of thrombosis.
91
What effect does smoking have on a fetus?
Although smoking increases the amount of fetal haemoglobin, the human fetus does not have a biological capacity to accommodate to maternal cigarette smoking, and therefore the fetus is particularly susceptible to the adverse effects of cigarettes.
92
What is emphysema?
The condition where the walls of the alveoli break down, so air sacs are fewer and larger.
93
Explain how emphysema can lead to death
- The breaking down of alveolar walls reduces the surface area available for gaseous exchange, causing fatigue and breathlessness.
- The lack of oxygen in tissues, especially the heart, can be a cause of death.
94
What are the main symptoms of emphysema?
Cough and shortness of breath.
95
How is emphysema detected?
- By measuring lung capacity with a spirometer.
- Diagnosis is confirmed with a chest X-ray and arterial blood gas analysis.
96
What are the causes of emphysema?
- Smoking (most important factor).
- Congenital (alpha-1 antitrypsin deficiency).
- Exposure to passive cigarette smoke.
- Air pollution.
- Occupational dust (for example in coal mines).
- Inhaled chemicals.
97
Explain the treatment for emphysema
- Treatment consists of the use of bronchodilators that cause dilation of bronchi, corticosteroids to reduce inflammation, oxygen supplementation, and antibiotics if there are signs of infection.
- This does not halt or cure the damage already done to the alveoli; it just alleviates the symptoms.
- The most important step is to quit smoking.
- Surgery or even lung transplant is done in very severe cases.
98
Diagram showing the oxygen dissociation curve of haemoglobin for a patient with emphysema
99
Where is the respiratory control center?
Medulla oblongata
100
How many peptide chains form a myoglobin molecule?
One
It consists of only one peptide chain and a heme group containing iron.
101
What is the main form of transport of carbon dioxide in blood?
As hydrogen carbonate (bicarbonate)
102
What is represented in the steep part of the oxygen dissociation curve of hemoglobin?
Oxygen is readily liberated at lower partial pressures of oxygen (in tissues).
