Respiratory physiology The Essentials Flashcards
(493 cards)
1
Q
Anatomic dead space
A
The conducting airways contain no alveoli and therefore take no part in gas exchange
2
Q
Respiratory bronchioles
A
The terminal bronchioles divide into respiratory bronchioles, which have occasional alveoli budding from their walls
3
Q
Respiratory zone
A
The alveolated region of the lung where the gas exchange occurs
4
Q
Acinus
A
the portion of lung distal to a terminal bronchiole forms an anatomical unit
5
Q
conducting zone
A
trachea, bronchi, bronchioles, terminal bronchioles
6
Q
Transitional and respiratory zones
A
Respiratory bronchioles, alveolar ducts, alveolar sacs
7
Q
Volume of the anatomic dead region in a human?
A
150 ml
8
Q
Volume of the alveolar region in a human
A
2,5-3 liters
9
Q
How is the main mechanism for movement in the alveolar region
A
By diffusion
10
Q
How big is the diameter of a capillary segment in a human?
A
7-10 um, just large enough for a red blood cell
11
Q
Consequences of the extreme thinness of the blood-gas barrier?
A
The capillaries (and thereby the blood-gas barrier) are easily damaged if too high pressure in the capillaries of if the lungs are inflated to high volumes: ultrastructural changes can then occur; The capillaries then leak plasma and ven red blood cells into the alveolar spaces
12
Q
Mean pulmonary arterial pressure required for a flow of 6 liter/min?
A
15 mm Hg (20 cm water)
13
Q
How long time does each red blood cell spend in the capillary network?
A
0,75 s and during this time probably traverses 2-3 alveoli (efficient gas exchange)
14
Q
Additional blood system of the lung?
A
The bronchial circulation: supplies the conducting airways down to about the terminal bronchioles (is a mere fraction of that through the pulmonary circulation. Some of theis blood is carried away from the lung via the pulmonary veins, and some enters the systemic circulation
15
Q
How is the thickness of much of the capillary walls?
A
less than 0,3 um
16
Q
How many alveoli approximately in the lungs
A
500 million in humans
17
Q
Surface area of the lungs in humans?
A
50-100 square meters
18
Q
Where is mucus secreted from?
A
By the mucus glands and also by glob let cells in the bronchial walls. The mucus i propelled by millions of tiny cilia
19
Q
Cilia in the alveoli?
A
No. Foreign material/particles that deposit there are engulfed by macrophages. The foreign material is then removed from the lungs via the lymphatics or the blood flow. Leukocytes also participate in the defense reaction to foreign material.
20
Q
When oxygen moves through the thin side of the blood-gas barrier from the alveolar gas to the hemoglobin of the red blood cell, it traverses the following layers in order
A
Surfactant, epithelial cell, interstitial, endothelial cell, plasma, red cell membrane
21
Q
How can tidal volume and vital capacity be measured
A
Simple spirometer
22
Q
How is total ventilation calculated?
A
Tidal volume x respiratory frequency
23
Q
What is the alveolar ventilation?
A
The amount of fresh gas getting to the alveoli
24
Q
What is the anatomic dead space
A
The volume of the conducting airways (150 ml in humans)
It increases with large inspirations (also depend on the size and the posture of the subject)
25
What is the physiologic dead space
The volume of gas that does not eliminate CO2 ( in normal subjects, the volumes are very nearly the same, however, in patients with lung disease, the physiologic dead space may be considerably larger because of inequality of blood flow and ventilation within the lung)
26
The 2 dead spaces (physiologic and anatomic) are almost the same in normal subjects, but the ........... dead space is increased in many lung diseases
The physiologic
27
Which volumes cannot be measured with a simple spirometer?
The goal lung capacity, the functional residual capacity, the residual volume
28
What is alveolar ventilation?
The volume of fresh (non-dead space) gas entering the respiratory zone per minute
29
How can the alveolar ventilation be determined?
Alveolar ventilation equation; CO2 output divided by the fractional concentration of CO2 in the expired gas
30
The concentration of .......in alveolar gas and the arterial blood is inversely related to the alveolar ventilation
CO2
31
What is the anatomic dead space?
The volume of the conducting airways (can be measured from the nitrogen concentration following a single inspiration of oxygen)
32
What is the physiologic dead space?
The volume of lung that does not eliminate CO2 (it is measured by Bohr's method using arterial and expired CO2
33
Why are the lower region of the lungs better ventilated than the upper regions?
Because of the effects of gravity on the lungs
34
Each acinus is supplied by........
a terminal bronchiole
35
Tidal volume
Volume/amount of air entering the lung with each inspiration (500 ml ca in humans). Normal breathing
36
Vital capacity
The subject takes a maximal inspiration and followed this by a maximal expiration. The exhaled volume is called the vital capacity
37
Residual volume
The gas remained in the lung after a maximal expiration.
38
Functional residual capacity (FRC)
The volume of gas in the lung after a normal expiration
39
Which lung volumes cannot be measured with the spirometer
Total lung capacity, functional residual capacity, residual volume
40
Total ventilation
The total volume leaving the lung each minute. (The volume of air entering the lung is very slightly greater because more oxygen is taken in than carbon dioxide is given out)
41
Alveolar ventilation
The volume of fresh gas entering the respiratory zone each minute (represents the amount of fresh inspired air available for gas exchange)
42
How can dead space ventilation be calculated?
Volume x Respiratory frequency.
43
How can the total volume of the anatomic dead space be measured?
Dead space ventilation (Volume x Respiratory frequency) is subtracted from the total ventilation.
44
At rest, the PO2 of the blood virtually reaches that of the alveolar gas after about .......... of its time in the capillary
one-third
45
Blood spends only about......second in the capillary at rest
0,75 second
46
Blood spends about......second in the capillary on exercise
0.25 second
47
The diffusion process is challenged by?
exercise, alveolar hypoxia and thickening of the blood-gas barrier
48
The reaction rate of O2 with HB is fast; so why can the rate become a limiting factor?
Because so little time is available in the capillary
49
The resistance to the uptake of O2 attributable to reaction rate is probably about the same as ...........
that due to diffusion across the blood-gas barrier
50
How can the reaction rate of CO with Hb be altered?
By changing the alveolar PO2
51
Fick's law
The rate of diffusion of a gas through a tissue sheet is proportional to the area of the sheet and the partial pressure difference across it, and inversely proportional to the thickness of the sheet.
52
Exempl. of diffusion -and perfusion-limited gases
Carbon monoxide and nitrous oxide.
Oxygen transfer is normally limited, but some diffusion limitation may occur under some conditions, including intense exercise, thickening of the blood-gas barrier, and alveolar hypoxia.
53
Diffusion capacity of the lung is measured using inhaled carbon monoxide. When does the value increase markedly?
During exercise
54
What can the finite reaction of oxygen with hemoglobin lead to?
Reduced transfer rate into the blood. The effect is similar to that of reducing the diffusion rate.
55
Is the carbon dioxide transfer across the blood-gas barrier diffusion limited?
Probably not
56
In a normal person; doubling the diffusion capacity of the lung would be expected to increase maximal oxygen uptake...when?
At extreme altitude for example.
57
Carbon monoxide is a diffusion limited gas, and so it is transferred into the blood along the whole length of the capillary, and there is a large difference in partial pressure between alveolar gas and end-capillary blood. What about nitrous oxide?
The opposite is true for nitrous oxide.
58
Breathing oxygen ........... the measured diffusing capacity for carbon monoxide compared with air breathing
Breathing oxygen reduces the measured diffusing capacity for carbon monoxide compared with air breathing
59
What happens with the diffusing capacity of the lung for carbon monoxide in a normal subject that exercise?
It increases
60
How does all gases move across the alveolar wall?
By passive diffusion
61
Why does CO2 diffuse about 20 times more rapidly than O2 through tissue sheets?
Because it has a much higher solubility but not a very different molecular weight
62
Why is the transfer of carbon monoxide in the lungs said to be "diffusion limited"
Carbon monoxide moves rapidly across the extremely thin blood-gas barrier from the alveolar gas into the cell. However, because of the tight bond that forms between carbon-monoxide and hemoglobin within the cell, a large amount of carbon monoxide can be taken up by the cell with almost no increase in partial pressure. Thus as the cell moves through the capillary, the carbon monoxide partial pressure in the blood hardly changes, and the gas continues to move rapidly across the alveolar wall. Accordingly; the amount of carbon monoxide that gets into the blood is limited by the diffusion properties of the blood-gas barrier and not by the amount of blood available.
63
Why is the transfer of nitrous oxide in the lungs said to be "perfusion limited"
Fig 3-2
When this gas moves across the alveolar wall into the blood, no combination with hemoglobin takes place. As a result, the blood has nothing like the avidity for nitrous oxide hat it has for carbon monoxide, and the partial pressure of nitrous oxide in the blood has virtually reached that of the alveolar gas by the time the red cell is only 1/10 of the way along the capillary. After this point; almost no nitrous oxide is transferred. Thus the amount of this gas taken up by the blood depends entirely on the amount of available blood flow and not at all on the diffusion properties of the blood-gas barrier.
64
Is the transfer of O2 in the lungs said to be "perfusion limited" or diffusion limited?
The time course of O2 lies between those of carbon monoxide and nitrous oxide. O2 combines with Hb (unlike nitrous oxide) but with nothing like the avidity of carbon monoxide. Accordingly, the rise in partial pressure when O2 enters a red blood cell is much greater than when the same numbers of carbon monoxide molecules enters. Under some conditions, transport of O2 can be perfusion limited, under other conditions it can be diffusion limited
65
Under which condition can the O2 transfer be perfusion limited?
The PO2 of the red blood cell as it enters the capillary is already abuts 4/10 of the alveolar value because of the O2 in mixed venous blood. Under typical resting conditions, the capillary PO2 virtually reaches that of alveolar gas when the red cell is about 1/3 of the way along the capillary. Under these conditions, O2 transfer is perfusion limited like nitrous oxide.
66
Under which condition can the O2 transfer be diffusion limited?
In some abnormal circumstances when the diffusion properties of the lungs are impaired, for example because of thickening of the blood-gas barrier, the blood PO2, does not reach the alveolar value by te end of the capillary, and now there is some diffusion limitation as well
67
What is the PO2 in a red blood cell entering the capillary normally?
40 mmHg
68
What is the alveolar PO2? How far doe the red cell need to travel in the capillary before reaching nearly the PO2 of alveolar gas?
100 mmHg after only 0,3 um after entering the blood-gas barrier. The PO2 in the red cell rapidly rises and nearly reaches the PO2 of alveolar gas by the tie the red cell is only 1/3 of its way along the capillary. Accordingly; the diffusion reserves of the normal lung are enormous
69
With severe exercise; the pulmonary blood flow is greatly increased. How does this influence the time normally spend by the red cell in the capillary?
Reduced from 0,75 s to as little as 1/3 of this. Therefore; the time available for oxygenation is less; but in normal subjects breathing air; there is generally still no measurable fall in end-capillary PO2.
70
What can happen with PO2 level in the alveolar gas and the capillary blood if the blood-gas barrier is markedly thickened by disease so that oxygen diffusion is impeded.
The rate of rise of PO2 in the red blood cells is correspondingly slow, and the PO2 may not reach that of alveolar gas before the time available for oxygenation in the capillary has run out. In this case: a measurable difference between alveolar gas and end-capillary blood for PO2 may occur.
71
What influences whether a gas is diffusion limited or not?
It depends essentially on its solubility in the blood-gas barrier compared with its solubility in blood. For a gas like carbon monoxide, these are very different, whereas for a gas like nitrous oxide, they are the same.
72
What happens during severe exercise if the alveolar PO2 is lowered? (for example due to high altitude or due to inhaling a low O2 mixture)
The partial pressure difference responsible for driving the O2 across the blood-gas barrier has been reduced (fig 3-3A). O2 therefore moves across more slowly. In addition, the rate of rise of PO2 for a given increase in O2 concentration in the blood is less than it was because of the steep slope of the O2 dissociation curve when the PO2 is low. For both these reasons; therefor, the rise in PO2 along the capillary is relatively slow, and failure to reach the alveolar PO2 is more likely.
Thus severe exercise at very high altitude is one of the few situations in which impairment of O2 transfer in normal subjects can be convincingly demonstrated. Alos patients with a thickened blood-gas barrier will most likely show evidence of diffusion impairment if they breathe a low oxygen mixture, especially if they exercise as well.
73
What can limit oxygen transfer into the pulmonary capillary?
Amount of blood flow available, but under som circumstances diffusion limitations also occurs.
74
What can limit carbon monoxide transfer?
Solely diffusion (it is therefore the gas of choice for measuring the diffusion properties of the lung)
75
DL: diffusion capacity of the lung equation includes the following:
area, thickness, and diffusion properties of the sheet and the gas concerned.
76
What can challenge the diffusion process?
Exercise, alveolar hypoxia, and thickening of the blood-gas barrier
77
Why is carbon monoxide often used for measurement of diffusion capacity?
Because the uptake of the carbon monoxide gas is diffusion limited.
78
How does exercise influence the diffusion capacity?
the diffusion capacity increases because of recruitment and distension of pulmonary capillaries
79
Does all the resistance to movement of O2 and CO2 resides in the barrier between blood and gas?
No, the path length from the alveolar wall to the center of a red blood cell exceeds that in the wall itself, so that some of the diffusion resistance is located within the capillary.
Also, resistance is caused by finite rate of reaction of O2 or CO with hemoglobin inside the red blood cell.
80
How fast is the combination of O2 (or CO) with Hb in the blood after adding into the blood?
< 0.2 seconds
81
The uptake of O2 (or CO) can be regarded as occurring in 2 stages. Which?
1) diffusion of O2 through the blood-gas barrier (including the plasma and red cell interior)
2) Reaction of the O2 with Hb.
It is possible to sum the 2 resultant resistances to produce an overall "diffusion" resistance
82
How is the diffusion capacity on the lung defined?
Effective diffusion capacity?
Total diffusion resistance?
Flow of gas divided by pressure difference.
Effective diffusion capacity: rate of reaction of O2 with Hb
Total diffusion resistance: The resistance offered by the membrane and the blood.
83
What influences the measured diffusing capacity of the lung for CO?
Area and thickness of the blood-gas barrier and also the volume of blood in the pulmonary capillary. Furthermore, in the diseased lung, the measurement is affected by the distribution of diffusion properties, alveolar volume, and capillary blood.
84
Why is diffusion of CO2 through tissue about 20 times fast than that of O2?
Because of the much higher solubility of CO2 (but also CO2 can be affected by diffusion difficulties if the blood-gas barrier is diseased).
85
Describe how the pulmonary artery further branches in the lungs
The artery branches successively like the system of airways, and the pulmonary arteries accompany the airways as fas as the terminal bronchioles. Beyond that, they break up to supply the capillary bed that lies in the walls of the alveoli. The pulmonary capillaries form a dense network in the alveolar wall that makes an exceedingly efficient arrangement for gas exchange. The oxygenated blood is the collected from the capillary bed by the smal pulmonary veins that run between the lobules and eventually unite to form the four large veins (humans), which drain into the left atrium.
86
How high is the mean pressure in the main pulmonary artery?
About 15 mmHg
87
How high is the systolic and diastolic pressure in the main pulmonary artery?
"5 and 8 mmHg respectively
88
Mean pressure in the aorta?
About 100 mmHg
89
Pressures in the right and left atriums?
Not very dissimilar: 2 and 5 mmHg, respectively
90
How is the pressure differences from inlet to outlet of the pulmonary and systemic systems?
15-5 = 10 and 100-2 = 98 mmHg, respectively ---A factor of 10.
91
How is the walls of the pulmonary artery and its branches?
Remarkably thin, and contain relatively little smooth muscle (easily mistaken for veins); striking contrast to the systemic cirkulation (easily mistaken for veins). This is of value as the lung is required to accept the whole of the cardiac output at all times, and rarely is concerned with directing blood from one region to another (only if there is localized alveolar hypoxia). This keeps the work of the right heart as small as feasible for efficient gas exchange to occur in the lung
92
How is the pressure within the capillaries?
Uncertain. But the pressure within the pulmonary capillaries varies considerably throughout the lung because of hydrostatic effects.
93
What is the transmural pressure?
The pressure difference between the inside and outside the capillaries. (there is a very thin layer of epithelial cells lining the alveoli, but the capillaries receive little support from this, and consequently, are liable to collapse or distend, depending on the pressures within and around them: This is very close to the alveolar pressure which is very close to the atmospheric pressure)
94
What is the pressure around the pulmonary arteries and veins?
Considerably less than alveolar pressure. As the lungs expands, these larger blood vessels are pulled open by the radial traction of the elastic lung parenchyma that surrounds them (effective pressure around them is low), and both the arteries and veins increase their caliber as the lung expands.
95
Which vessels are the "alveolar vessels"?
| What determines their caliber?
Capillaries and the slightly larger vessels in the corners of the alveolar walls. Their caliber is determined by the relationship between alveolar pressure and the pressure within them. Alveoler vessels are compressed if the alveolar pressure increase
96
Which are the extra-alveolar vessels?
The arteries and veins that run through the lung parenchyma. Their caliber is greatly affected by lung volume. Extra-alveolar vessels are exposed to a pressure less than alveolar and are pulled open by the radial traction of the surrounding parenchyma. The very large vessels near the hilum are outside the lung substance and are exposed to intrapleural pressure.
97
How is vascular resistance defined/calculated?
Input pressure-output pressure/blood flow
98
Identical blood flows through the two circulations, but total pressure drop from pulmonary artery to left atrium in the pulmonary circulation is only some 10 mmHg, against about 100 mmHg for the systemic circulation. How is the pulmonary vascular resistance in comparison to the systemic circulation?
About 1/10 that of the systemic circulation.
99
What is the high resistance of the systemic circulation largely a result of? Why a different in the pulmonary circulation?
Very muscular arterioles that allow the regulation of blood flow to various organs of the body.
The pulmonary circulation has no such vessels and appears to have as low resistance as is compatible with distributing the blood in a thin film over a vast area in the alveolar walls.
100
The normal pulmonary vascular resistance is extraordinary small. What happens with the pressure if the pressure within the vessels rises?
The resistance becomes even smaller. An increase in either pulmonary arterial or venous pressure causes pulmonary vascular resistance to fall.
101
Which 2 mechanisms are responsible for the drop in pulmonary vascular resistance if there is an increase in either pulmonary arterial or venous pressure (such as during exercise)?
1) The chief mechanism: Opening of previously closed vessels as the pressure rises; these vessels begin to conduct blood; thus lowering the overall resistance (= recruitment)
2) At higher vascular pressures, widening of individual capillary segments occurs (distension). Change from near-flattened to more circular.
Recruitment and dissension often occurs together.
102
In which scenarios is the resistance in the extra-alveolar influenced (high resp low resistance)?
The caliber of the extra-alveolar vessels is determined by a balance between various forces. They are pulled open as the lung expands. As a result; their vascular resistance is low at large lung volumes. On the other hand, their walls contain smooth muscle and elastic tissue, which resist distention and tend to reduce the caliber of the vessels. Consequently; they have a high resistence when the lung volume is low.
103
What is "critical opening pressure"?
If the lung is completely collapsed; the smooth muslce tone of the vessels is so effective that the pulmonary arty pressure has to be raised several centimeters of water above downstream pressure before any flow at all occurs= critical opening pressure.
104
Is the vascular resistance of the capillaries influenced by lung volume?
If alveolar pressure rises with respect to capillary pressure, the vessels tend to be squashed, and their resistance rises: this usually occurs when a normal subject takes a deep inspiration, because the vascular resistance fall (the heart is surrounded by intrapleural pressure, which falls on inspiration. In addition; the caliber of the capillaries is reduced at large lung volumes because of stretching and consequent thinning of the alveolar walls. Thus, even if the transmural pressure of the capillaries is not changes with large lung inflations, their vascular resistance increases
105
Why do drugs that cause contraction of muscles increase pulmonary vascular resistance?
Because of the role of smooth muscle in determining the caliber of the extra-alveolar vessels.
106
Examples of drugs that cause contraction of muscles leading to increased pulmonary vascular resistance?
Histamine, serotonin, norepinephrine. These drugs are particularly effective vasoconstrictors when the lung volume is low,a d the expanding forces on the vessels are weak.
107
Example of drugs that can relax smooth muscle in the pulmonary circulation?
Acetylcholine and isoproterenol
108
How does high and low lung volume influence the pulmonary vascular resistance?
The pulmonary vascular resistance increases
109
Why does the pulmonary vascular resistance increase with alveolar hypoxia?
Because of constriction of small pulmonary arteries
110
Fick principle:
Estimation of the volume of blood passing through the lungs each minute (O2 consumption per minute measured at the mouth is equal to the amount of O2 taken up by the blood in the lungs per minute.
111
What can explain the uneven distribution of blood flow?
The hydrostatic pressure differences within the blood vessels.
112
If we consider the pulmonary arterial system as a continuous clump of blood, the difference in pressure between the top and bottom of a lung 30 cm high (human) will be about .....mmHg
23 mmHg. Accordingly; there may be a region (zone 1) at the top of the lung where pulmonary arterial pressure falls below alveolar pressure (normally close to atmospheric pressure). If this occurs; the capillaries are squashed flat, and no flow is possible (humans at least...). However this does not occur under normal conditions, because the pulmonary arterial pressure is just sufficient to raise blood to the top of the lung., but may be present if arterial pressure is reduced (following severe hemorrhage for example or if alveolar pressure is raised)
113
How is the pulmonary arterial pressure in zone 2 compared to the alveolar pressure?
Pulmonary arterial pressure exceeds alveolar pressure in this zone (humans). Under these conditions, blood flow is determined by the difference between arterial and alveolar pressures (not the usual arterial -venous pressure difference). Indeed, venous pressure has no influence on flow unless it exceeds alveolar pressure.
114
How is the venous pressure compared to the alveolar pressure in zone 3?
Venous pressure here exceeds alveolar pressure, and flow is determined in the usual way by the arterial-venous pressure difference. The increase in blood flow down this region of the lung is apparently caused chiefly by dissension of the capillaries. The pressure within them (lying between arterial and venus) increases down the zone, while the pressure outside (alveolar) remains constant. Recruitment of previously closed vessels may also play some part in the increase in blood flow down this zone.
115
Other factors than zone 1-3 causing unevenness of blood flow in the lung?
Partly random arrangement of blood vessels and capillaries at any given level in the lung.
Blood flow decreases along the acinus: with peripheral parts less well supplied with blood.
Peripheral regions of the whole lung may receive less blood flow than the central regions.
Some regions of the lung may have an higher vascular resistance.
116
What does "hypoxic pulmonary vasoconstriction" mean?
Contraction of smooth muscle in the walls of the small arterioles in the hypoxic region (unknown precise mechanism of this response). Does not depend on CNS connections. Local action on the artery itself. The PO2 of the alveolar gas, not the pulmonary arterial blood, chiefly determines the response.
117
The vessel wall becomes hypoxic as a result of diffusion of oxygen over the very short distance from the wall to the surrounding alveoli. How does an alveolar PO2 in the region above 100 mmHg, below approximately 70 mmHG, and at very low PO2 influence the vascular resistance?
100 mmHg; little changes in vascular resistance
118
How does Nitric oxide (NO) influence blood vessels? What is NO formed from?
Endothelium-derived relaxing factor for blood vessels. It is formed from L-arginine via catalysis by endothelial NO synthase (eNOS)
119
How does NO act?
NO increases the synthesis of cyclic GMP; which leads to smooth muscle relaxation
120
How does inhaled NO act in scenarios of hypoxic pulmonary vasoconstriction in humans?
Reduces the hypoxic pulmonary vasoconstriction.
121
Influence of alveolar hypoxia on small pulmonary arteries?
Causes constriction of small pulmonary arteries (probably a direct effect of the low PO2 on vascular smooth muscle)
122
How does the pulmonary vascular endothelial cell released endothelia-1 (ET-1) and thromboxane A2 (TXA2) influence vessels in the lungs
Potent vasoconstrictors.
| Blockers of endothelia receptors have been used clinically to treat patients with pulmonary hypertension.
123
How can hypoxic vasoconstriction influence scenarios with hypoxic regions of lung?
Has the effect of directing blood away from hypoxic regions of lung. These regions may be result from bronchial obstruction, and by diverting blood flow, the deleterious effects on gas exchange are reduced.
124
How does high altitude influence pulmonary vessels/blood flow?
Generalized pulmonary vasoconstriction occurs, leading to a rise in pulmonary arterial pressure.
125
During fetal life, the pulmonary vascular resistance is very high, partly because of hypoxic vasoconstriction, and only some 15 % of the cardiac output goes through the lungs. What occurs when the first breath oxygenates the alveoli?
The vascular resistance falls dramatically because of relaxation of vascular smooth muscle, and the pulmonary blood flow increases enormously.
126
How does a low blood pH influence the pulmonary circulation?
Causes vasoconstriction, especially when alveolar hypoxia is present.
127
How does the autonomic nervous system influence the pulmonary circulation?
Exerts a weak control; an increase in sympathetic outflow causing stiffening of the walls of the pulmonary arteries and vasoconstriction.
128
Fluid exchange across the capillary endothelium obeys Starling's law. Which force tend to push fluid out of the capillary?
The capillary hydrostatic pressure minus the hydrostatic pressure in the interstitial fluid (Pc- Pi).
129
Which force tend to pull fluid in to the capillaries?
The colloid osmotic pressure of the proteins of the blood minus that of the proteins of the interstitial fluid. This force depends on the reflection of a coefficient; which is a measure of the effectiveness of the capillary wall in preventing the passage of proteins across it.
130
What is the colloid osmotic pressure within the capillary?
| And of the lung lymph (interstitial fluid not known)
About 25-28 mmHg within the capillary and about 20 mmHg in lung lymph (interstitial fluid not known)
131
How is the interstitial hydrostatic pressure in relation to the atmospheric pressure?
The interstitial hydrostatic pressure is unknown, but it is substantially below the atmospheric pressure.
132
Where does fluid go when it leaves the capillaries?
The fluid leaks out into the interstitial of the alveolar wall
tracks through the interstitial space to the perivascular and peribronchial space within the lung. Numerous lymphatics run in the perivascular spaces, and these help to transport the fluid to the hilar lymph nodes. In addition, the pressure in the perivascular spaces is low, thus forming a natural sump for the drainage of fluid.
133
What characterize the earliest form of pulmonary edema?
Engorgement of the peribronchial and perivascular spaces and is known as interstitial edema.
134
How is the rate of lymph flow from the lung influenced if the capillary pressure is raised over a long period?
The rate of lymph flow increases considerably
135
What characterize a later stage of pulmonary edema?
Fluid may cross the alveolar epithelium into the alveolar spaces. When this occurs, the alveoli fill with fluid one by one, and because they are then unventilated, no oxygenation of the blood passing through them is possible.
136
What prompts fluid to start moving across into the alveolar spaces?
This is not known, but it may be that this occurs when the maximal drainage rate through the interstitial space is exceeded and the pressure there rises too high.
137
What happens with fluid that reaches the alveolar space?
The fluid is actively pumped out by a sodium-potassium ATPase pump in epithelial cells.
138
Why is alveolar edema is much more serious than interstitial edema?
Alveolar edema is much more serious than interstitial edema because of the interference with pulmonary gas exchange.
139
Important functions of the pulmonary circulation?
| 4
1. Move blood to and from the blood-gas barrier so that gas exchange can occur.
2. Act as a reservoir for blood. Pulmonary recruitment and distension allow the lung to increase its blood volume with relatively small rises in pulmonary arterial or venous pressures. (this occurs, for example, when a subject lies down after standing; Blood then drains from the legs into the lung).
3. Filter blood. Small thrombi are removed from the circulation before they can reach the brain or other vital organs. Also many white blood cells are trapped by the lung and later released (value unknown).
140
Metabolic function of the lung: A number of vasoactive substances are metabolized by the lung (the lung is the only organ except the heart that receives the whole circulation; and it is therefore uniquely suited to modify bloodborne substances). But what is the only known example of biological activation by passage through the pulmonary circulation? What catalyze this process?
The conversion of the relatively inactive polypeptide angiotensin I to the potent vasoconstrictor angiotension II. The latter, which is up to 50 times more active than its precursor, is unaffected by passage through the lung.
The conversion of angiotensin I is catalyzed by angiotensin converting enzyme, or ACE, which is located in small pits in the surface of the capillary endothelial cells.
141
Many vasoactive substances are completely or partially inactivated during passage through the lung. Bradykinin is largely inactivated (up to 80%), and the enzyme responsible is .....?
ACE
142
The lung is the major site of inactivation of serotonin (5-HT), but this is not by enzymatic degradation. But how?
By an uptake and storage process. Some of the serotonin may be transferred to platelets in the lung or stored in some other way and released during anaphylaxis.
143
What occurs with prostaglandins E1, E2, and F2alpha in the lungs?
Become inactivated.
144
What occurs with norephinephrine in the lungs?
Taken up by the lung to some extent (up to 30%)
145
What occurs with histamine in the lungs?
Appears not to be affected by the intact lung
146
Example of vasoactive materials that can pass through the lung without significant gain or loss of activity?
Epinephrine, prostaglandins A1 and A2, angiotension II, and vasopressin (ADH).
147
Several vasoactive and bronchoactive substances are metabolized in the lung and may be released into the circulation under certain conditions. Important among these are the............metabolites
Arachidonic acid metabolites.
148
How is arachidonic acid form?
| Fig 4-12
Through the action of the enzyme phospholipase A2 on phospholipid bound to cell membranes. There are 2 major synthetic pathways: the initial reactions being catalyzed by the enzymes lipooxygenase (producing the leukotrienes) and cyclooxygenase (producing the prostaglandins and thromboxane A2), respectively.
149
Effects of leukotrienes, which include the mediator originally described as slow-reacting substances of anaphylaxis (SRS-A) on the airways?
Airway constriction and may have an important role in asthma. Other leukotrienes are involved in inflammatory responses.
150
Does prostaglandin have vasoconstrictor of vasodilator effects?
Prostaglandins are potent vasoconstrictors OR vasodilators
151
Important role of prostaglandin E2 effect in the fetus?
Plays an important role in the fetus because it helps to relax the PDA.
152
Other important roles of prostaglandins (beside vasoconstriction/vasodilation)?
Affect platelet aggregation and are active in other systems, such as the kallikrein-kinin clotting cascade. They may also have a role in the bronchoconstriction of asthma.
153
There is evidence that the lungs plays a role in the clotting mechanism of blood under normal and abnormal conditions. One example?
There are large number of mast cells containing heparin in the interstitial.
154
How can the lung play an import function in the defense against infection?
The lung is able to secrete special immunoglobulins, particularly IgA, in the bronchial mucus that contribute to the defense against infection.
155
Synthetic functions of the lung?
Include the synthesis of phospholipid such as dipalmitoyl phosphatidylcholine (DPP), which is a component of pulmonary surfactant.
Protein synthesis is also clearly important because collagen and elastin form the structural framework of the lung.
156
Under some conditions, proteases are apparently liberated from leukocytes in the lung, causing breakdown of collagen and elastin. What can this process result in?
Emphysema
157
Carbohydrate metabolism is also important area for the lungs. Especially the elaboration of mucopolysaccharides of.....
....of bronchial mucus.
158
The pressurs within the pulmonary circulation are much lower than in the systemic circulation. Also the capillaries are exposed to alveolar pressure. How is the pressures around the extra-alveolar vessels?
The pressures around the extra-alveolar vessels are lower
159
The pulmonary vascular resistance is generally low. What happen with the pulmonary vascular resistance when cardiac output increases?
The pulmonary vascular resistance falls even more because of recruitment and dissension of the capillaries.
160
What happen with the pulmonary vascular resistance at very low or high lung volumes?
The pulmonary vascular resistance increases at very low or very high lung volumes.
161
Blood flow is unevenly distributed in the upright lung. There is a higher flow at the base than at the apex as a result of gravity. What happens with the capillaries if the capillary pressure is less than the alveolar pressure at the top of the lung?
The capillaries collapse and there is no blood flow (zone 1; humans),
162
Hypoxic pulmonary vasoconstriction reduces the blood flow to poorly ventilated regions of the lung. How is the influence of this effect important at birth?
Release of this mechanism is responsible for a large increase in blood flow to the lung at birth.
163
Fluid movement across the capillary endothelium is governed by the .......equilibrium.
The Starling equilibrium.
164
The ration of total systemic vascular resistance to pulmonary circulation is about
10:1
165
In zone 2 of the lung; Blood flow is determined by arterial pressure minus.............pressure
minus alveolar pressure
166
Pulmonary vascular resistance is reduced by acutely ............. pulmonary venous pressure.
increasing
167
2 relatively simple causes of of impairment of gas exchange.
Hypoventilation and shunt
168
The PO2 of air is -----% of the total dry gas pressure (excluding water vapor)
20.93%
169
Barometric pressure at sea level?
760mmHg
170
The fluctuation in alveolar PO2 with each breath is only about 3 mmHg. Why so small fluctuations?
Because the tidal volume is small compared with the volume of gas in the lung, so the process can be regarded as continuous.
171
In addition to small fluctuations in alveolar PO2; The rate of removal of O2 from the lung is governed by the consumption of O2 of the tissues, and varies little under resting conditions. In practice, therefore; the alveolar PO2 is largely determined by?
The level of alveolar ventilation. The same applies to the alveolar PCO2, which is normally about 40 mmHg.
172
4 causes of hypoxemia?
1. Hypoventilation
2. Diffusion limitation
3. Shunt
4. Ventilation-perfusion inequality.
173
Where does the O2 in the systemic arterial blood diffuse when reaching the tissue?
Into the mitochondria where the O2 is much lower.
174
How does an impaired pulmonary gas exchange influence the tissue pCO2?
Rise in PCO2
175
What is hypoventilation?
If the alveolar ventilation is abnormally low, the alveolar pO2 falls, and (both alveolar and arterial) PCO2 rises.
Hypoventilation decreases the P=2 unless additional O2 is inspired
176
Causes of hypoventilation?
- Drugs such as morphine and barbiturates thats depress the central drive to the respiratory muscles.
- Damage to the chest wall
- Paralysis of the respiratory muscles
- High resistance to breathing (for ex very dense gas at great depth underwater)
177
Hypoventiliation always reduced the alveolar and arterial PO2 except when?
When the subject breathes an enriched O2 mixture. In this case, the added amount of O2 per breath can easily make up for the reduced flow of inspired gas.
178
Why are the CO2 stores much greater than the O2 stores?
Because of the large amount of CO2 in the form of bicarbonate in the blood and interstitial fluid.
179
In a perfect lung, the PO2 of arterial blood would be the same as that in the alveolar gas. How big is the PO2 difference between alveolar gas and end-capillary blood resulting from incomplete diffusion under normal conditions? What can make the difference larger?
Immeasurably small under normal conditions. The difference can become larger
- during exercise
- when the blood-gas barrier is thickened
- if a low O2 mixture is inhaled.
180
What is a shunt?
Blood that enters the arterial system without going through ventilated areas of the lung
181
Can some blood enter the arterial system without going through ventilated areas of the lung also under normal conditions? (other than heart disease)
Yes, some bronchial artery blood is collected by the pulmonary veins after it has perfused the bronchi and its O2 has been partly depleted.
Another source is a small amount of coronary venous blood that drains directly into the cavity of the left ventricle through the thebesian veins.
(The effect of the addition of this poorly oxygenated blood is to depress the arterial PO2)
Some patients may also have an abnormal vascular connection between a small pulmonary artery and vein (pulmonary arteriovenous fistula)
182
How is the O2 concentration of end-capillary blood usually calculated?
From the alveolar PO2 and the oxygen dissociation curve
183
If a patient has a shunt; can the hypoxemia be ablished by giving the subject 100% O2 to breathe? Why is it so?
No, hyopoxemia responds poorly to added inspired O2. This is because the shunted blood that bypasses ventilated alveoli never is exposed to the higher alveolar PO2, so it continues to depress the arterial PO2.
However, some elevation of the arterial PO2 occurs because of the O2 added to the capillary blood of ventilated lung. Most of the added O2 is in the dissolved form, rather than attached to hemoglobin, because the blood that is perfusing ventilated alveoli is nearly fully saturated.
184
Why is giving the subject 100% O2 to breathe a very sensitive measurement of shunt?
When the 100% O2 is inspired, the arterial PO2 does not rise to the expected level; a useful diagnostic test.
Because when the PO2 is high, a small depression of arterial O2 concentration causes a relatively large fall in PO2 due to the almost flat slope of the O2 dissociation curve in this region. Fig 5-4
185
Does a shunt result in a raised PCO2 in arterial blood? Why?
No, usually not, even though the shunted blood is rich in CO2. The reason is that the chemoreceptors sense any elevation of arterial PCO2 and they respond by increasing the ventilation. This reduced the PCO2 of the unshunted blood until the arterial PCO2 is normal. However, in some patients with a shunt, the arterial PCO2 is low because the hypoxemia increases respiratory drive.
186
If the shunt is caused by mixed venous blood: how can its size be calculated?
It can be calculated from the shunt equation.
187
Ventilation-perfusion inequality is the most common cause of hypoxemia. What does it mean?
If ventilation and blood flow are mismatched in various regions of the lung, impairment of both O2 and Co2 transfer results. The key to understand how this happens is the ventilation-perfusion ratio.
188
The concentration of O2 (or better PO2) in any lung unit is determined by the ratio of ventilation to blood flow. Is this true not only for O2 but also for CO2, N2 and any other gas that is present under steady-state conditions?
yes. This is why the ventilation-perfusion ratio plays such a key role in pulmonary gas exchange.
189
Effect of altering the ventilation-perfusion ratio on the PO2 and PCO2: Effect of reduced ratio by obstructing its ventilation?
Decreased O2, Slightly increased CO2.
| Fix 5-7
190
Effect of altering the ventilation-perfusion ratio on the PO2 and PCO2: Effect of increasing ratio by gradually obstructing blood flow?
Increased O2, decreased CO2 (eventually reaching the composition of inspired gas when blood flow is abolished).
Fig 5-7
191
Effect of altering the ventilation-perfusion ratio on the PO2 and PCO2: Ventilation completely abolished (ventilation-perfusion ratio 0)?
O2 and CO2 of alveolar gas and end-capillar blood must be the same as those of mixed venous blood (in practice, completely obstructed units eventually collapse)
192
Where is the ventilation-perfusion ratio is abnormally high? At the top or at the bottom of the lung?
At the top of the lung where the blood flow is minimal. Much lower at the bottom Accordingly; regional differences in ventilation-perfusion ratio on an O2-CO2 diagram.
The ventilation-perfusion ratio decreases down the lung.
193
In an upright lung; PO2 of the alveoli decrease markedly down the lung (over 40mm Hg). What about the PCO2?
Increases much less (fig 5-9). Difference in PCO2 between apx and base is much less because this can be shown to be more closely related to ventilation.
(As a result; the respiratory exchange ratio (CO2 output/O2 uptake) is higher at the apex than at the base. On excercis when the distribution of blood flow becomes more uniform, the apex assume a larger share of the O2 uptake.
194
Can a lung with ventilation-perfusion inequality maintain as high an arterial PO2 r as low an arterial PCO2 as a homogenous lung?
No. The relative sizes of the airways and blood vessels are different in different regions. (most of the blood comes from the base, the relative size of the airways are larger at the apex). In addition; the lung units with a high ventilation perfusion ratio add relatively little oxygen to the blood, compared with the decrement (like depression of PO2 in other regions, and elevation of the PCO2) caused by alveoli with a low ventilation-perfusion ratio. The net effect is depression of arterial PO2 below that of the mixed alveolar PO2- the so-called alveolar-arterial O2 difference. In lung disease, the lowering of PO2 by this mechanism can be extreme.
195
How is the distribution of ventilation-perfusion ratios change in patients with for ex chronic bronchitis and emphysema? Fig 5-14
Although much of the ventilation and blood flow goes to compartments with ventilation-perfusion ratios near normal, considerable blood flow is gong to compartments with ventilation-perfusion ratios between 0.03-03 (instead of 1). Blood from these units will be poorly oxygenated and will depress the arterial PO2. There is also excessive ventilation to lung units with ventilation-perfusion ratios up to 10: these units are inefficient at eliminating CO2.
196
Mismatching of both ventilation and blood flows if everything else remained unchanged (however, not normally so)? (how is the O2 and CO2 affected in the body?)
Both hypoxemia and hypercapnia (CO2 retention). However, in practice, patients with ventilation-perfusion inequality often have a normal arterial pCO2. This is necessary as the lung units with abnormally high ventilation-perfusion ratios are inefficient at eliminating CO2 (alveolar dead space)
197
Why does patients with ventilation-perfusion inequality often have a normal arterial pCO2.
Whenever the chemorecpeotrs sense a rising pCO2; there is an increase in ventilatory drive. The consequent increase in ventilation to the alveoli is usually effective in returning the arterial PCO2 to normal.
198
Increase in ventilation to a lung with ventilation-perfusion inequality is usually effective at reducing the arterial PCO2: what about arterial PO2?
Much less effective at increasing the arterial PO2. (the reason for the different behavior of the two gases lies in the shapes of the CO2 and O2 dissociation curves. Se förklaring s 73. Those units that have a very ventilation-perfusion ratio continue to put out blood with an O2 conc close to that of mixed venous blood. The net result is that the mixed arterial PO2 rises only modestly, and some hypoxemia always remains.
199
What is the ventilation-perfusion ratio (VA/Q)
Determines the gas exchange in any single lung unit
200
VA/Q inequality leads to?
Impaired uptake or elimination of all gases by the lung
201
How can ventilation-perfusion inequality be assessed?
Assessing the alveolar-arterial PO2 difference. Abnormally high alveolar-arterial PO2 difference indicates that there is ventilation-perfusion inequality.
202
How is the alveolar-arterial PO2 difference obtained?
Subtracting the arterial PO2 from the so-called ideal alveolar PO2 (the ideal PO2 is that the lung would have if there were no ventilation-perfusion inequality, and it was exchanging gas at the same respiratory exchange ratio as the real lung.
203
two causes of hypercapnia (or CO2 retention)
Hypoventilation and ventilation-perfusion inequality
204
The only cause of hypoxemia in which the arterial PO2 does not rise to the expected leve when a patient is given 100% O2 to breathe.
A shunt
205
Ventilation-perfusion ratio determines the PO2 and PCO2 in any lung unit. Why i PO2 high and PCO2 low at the top of the lung
Because the ratio is high there
206
How can alveolar PO2 be calculated for use in the alveolar-arterial equation?
From the alveolar gas equation using the arterial PCO2
207
Which 2 forms are O2 carried in?
Dissolved and combined with Hb
208
Dissolved O2 obeys Henry's law. Which means?
The amount dissolved is proportional to the partial pressure. For each mmHG of Po2 there is a certain ml of O2 in the blood. A normal arterial blood with a PO2 of 100mm HG contains 0.3 ml 02 100 ml-1.
It is easy to see that this way of transporting =2 is inadequate. Additional method is required.
209
What is heme?
An iron-prophyrin compound: this is joined to the protein globin, which consists of 4 polypeptide chains.
210
2 types of chains in the hemoglobin?
alpha and beta. Differences in their amino acid sequences give rise to various types of hemoglobin
211
Normal adult hemoglobin?
A
212
What is hemoglobin F?
Fetal hemoglobin. This is gradually replaced over the first year of the postnatal life
213
Hemoglobin S? Consequence?
Sickle. Hb S has valine instead of glutamic acid in the beta chains. This results in a reduced O2 affinity and a shift in the dissociation curve to the right, but more important, the deoxygenated form is poorly soluble and crystallizes within the cell. As a consequence; the cell shape changes from biconcave to crescent or sickle shaped with increased fragility and a tendency to thrombus formation.
214
Normal hemoglobin A can have its ferrous ion oxidized to the ferric form (methemoglobin) by various drugs and chemicals: which?
Nitrites, sulfonamides and acetanilid
215
There is a congenital cause in which the enzyme methemoglobin reductase is deficient within the red blood cell. Another abnormal form is sulfhemoglobin. Can these compounds carry O2?
No, these compounds are not useful for O2 carriage.
216
O2 forms an easily reversible combination with Hb to give oxyhemoglobin. Which?
O2 + Hb ---HbO2
217
O2 capacity?
The maximum amount of O2 that can be combined with Hb. This is when all the available binding sites are occupied by O2. It can be measured by exposing the blood to a very high PO2, and subtracting the dissolved O2.
218
O2 saturation of Hb?
The percentage of the available binding sites that have =2 attached. O2 combined with Hb/O2 capacity x 100
219
Approximate O2 saturation of arterial blood with PO2 of 100 mmHg
97,5%
220
Approximate O2 saturation of mixed venous blood with a PO2 of 40 mmHg?
75%.
221
What is the R state resp T state of the Hb molecule?
R state = relaxed state= oxygenated state
T = tense state = deoxy form
The change in Hb from the fully oxygenated state to its deoxygenated state is accompanied by a conformational change in the molecule.
222
A severely anemic patient has normal lungs and an arterial PO2 of 100 mmHg. Can this patient have a normal O2 saturation of 97,5%, normal pH, PCO2 and temperature?
Yes
223
The curved shape of the O2 dissociation curve has several physiological advantages. What advantage does the flat upper portion have in case of falling PO2 in alveolar gas?
Even if the PO2 in alveolar gas falls somewhat, loading of O2 will be little affected.
In addition, as the red cell takes up O2 along the pulmonary capillary, a large partial pressure difference between alveolar gas and blood continues to exist when most of the O2 has been transferred.
224
Reduced Hb is purple; accordingly; a low arterial O2 saturation causes......?
Cyanosis.
225
Why is cyanosis often marked when polycythemia is present, but difficult to detect in anemic patients?
Because it is the amount of reduced Hb that is important.
226
When the O2 dissociation curve is shifted to the right; the O2 affinity of Hb is......
reduced
227
Why is the O2 affinity of Hb reduced when the O2 curve is shifted to the right?
By an
- increase in H+ concentration
- increase in PCO2
- increase in temperature
- increase in conc of 2,3-diphosphoglycerate in the red cell
228
What causes a shift of the O2 dissociation curve to the left?
By an
- decrease in H+ concentration
- decrease in PCO2
- decrease in temperature
- decrease in conc of 2,3-diphosphoglycerate in the red cell
229
Most of the effect of PCO2 (influencing the dissociation curve), which is known as the Bohr effect, can be attributed to its action on..........concentration
its action on H+ concentration.
230
A rightward shift means ........unloading of O2 at a given PO2 in a tissue capillary.
A rightward shift means more unloading of O2 at a given PO2 in a tissue capillary.
231
A simple way to remember the shifts of the O2 dissociation curves? An exercising muscle is acid, hypercarbic and hot, and it benefits from ...........
An exercising muscle is acid, hypercarbic and hot, and it benefits from increased unloading of O2 from its capillaries.
232
The environment of the Hb within the red cell also affects the O2 dissociation curve. An increase in 2,3-diphosphoglycerate (DPG) shifts the curve to the right. What is the 2,3-DPG?
An end-product of red cell metabolism
233
When does the concentration of 2,3-DPG increase
In chronic hypoxia, for example at high altitude or in the presence of chronic lung disease. As a result, the unloading of O2 to peripheral tissue is assisted.
234
What can cause a depletion of 2,3-DPG? Consequence?
Stored blood in a blood bank. Unloading of O2 is therefore impaired
235
A useful measure of the position of the dissociation curve?
P50. A useful measure of the position of the dissociation curve is the PO2 for 50% O2 saturation. (the normal value for human blood is about 27 mmHg.
236
Useful anchor points (human) PO2 40, SO2......
| PO2 100, SO2....
PO2 40, SO2 75%
| PO2 100, SO2 97,5%
237
Small addition of CO to blood causes a..... of the O2 dissociation curve
A left shift of the O2 dissociation curve.
238
How does carbon monoxide (CO) interfere with the O2 transport function of blood?
By combining with Hb to form COHb
239
How is the affinity of O2 for CO compared to Hb
CO has about 240 times the affinity of O2 for Hb, this means that CO will combine with the same amount of Hb as O2 when the CO partial pressure is 240 times lower.
240
How is the shape of the CO dissociation curve compared to the O2 curve?
Almost identical in shape to the O2 dissociation curve, except that the PCO axis is greatly compressed. For ex at a PCO of 0,16 mmHG, about 75% of the Hb is combined with CO as COHb. For this reason; small amounts of CO can tie up a large proportion of the Hb in the blood; thus making it unavailable for O2 carriage.
241
small amounts of CO can tie up a large proportion of the Hb in the blood; thus making it unavailable for O2 carriage. How does this happens; how will this influence the Hb conc and PO2 of blood?
The Hb conc and PO2 of blood may be normal, but its O2 conc is grossly reduced. The presence of COHb also shifts the O2 dissociation curve to the left, thus interfering with the unloading of O2. This is an additional feature of the toxicity of CO
242
In which 3 forms is CO2 carried in the blood?
Dissolved, as bicarbonate and in combination with proteins as carbamino compounds. The great bulk of CO2 is in the form of bicarbonate.
243
Dissolved CO2 like O2 obeys Henry´s law. But how is the solubility of CO2 compared to O2?
CO2 is about 20 times more soluble than O2. As a result, dissolved CO2 plays a significant role in its carriage in that abut 10% of the gas that is envolved into the lung from the blood is in the dissolved form.
244
Bicarbonate is formed in the blood by the following sequence:
CO2 + H20 ---H2CO3---H+ + HCO3-
245
The first reaction: CO2 + H20 ---H2CO3 is very slow in plasma but fast within the red blood cell. Why?
Because of the presence there of the enzyme carbonic anhydrase (CA).
(The second reaction, ionic dissociation, H2CO3---H+ + HCO3-, is fast without enzyme)
246
When the concentration of these ions (CO2 + H20 ---H2CO3---H+ + HCO3-) rises within the red cell; what occurs then?
HCO3- diffuses out, but H+ cannot easily do this because the cell membrane is relatively impermeable to cations.
247
What is the chloride shift?
HCO3- diffuses out easily, but H+ cannot easily do this because the cell membrane is relatively impermeable to cations. Thus, to maintain electrical neutrality, Cl- ions move into the cell from the plasma = chloride shift.
248
Some of the H+ ions liberated are bound to reduced hemoglobin
H+ + HbO2 ----H+. Hb + O2
This occurs because reduced Hb is less acid (that is, a better proton acceptor) than the oxygenated form. Thus the presence of reduced Hb in the peripheral blood helps with loading of CO2, whereas the oxygenation that occurs in the pulmonary capillary assists in the unloading.
249
What is the Haldane effect?
Deoxygenation of the blood increases its ability to carry CO2.
250
Uptake of CO2 by blood increase the osmolar content of the red cell, and consequently, waters enters the cell; thus increasing its volume. What happens when the cell pass throughout the lung?
They shrink a little
251
How are carbamino compounds formed?
By the combination of CO2 with terminal amine groups in blood proteins. the most important protein is the glob in of hemoglobin: HbNH2 + CO2---Hb.NH.COOH: giving carbinohemoglobin. This reaction occurs rapidly without an enzyme, and reduced Hb can bind more CO2 as carbaminohemoglobin than HBO2.
Thus again, unloading of O2 in peripheral capillaries facilitates the lading of CO2 whereas oxygenation has the opposite effect.
252
How is the CO2 dissociation curve compared to the O2 dissociation curve?
Much more linear.
The CO2 dissociation curve is also considerably steeper than that for O2. This is why the PO2 difference between arterial and mixed venous blood is large (typically about 60 mmHG) but the PCO2 difference is small (about 5 mmHg)
253
Moreover; the lower the saturation of Hb with O2, the ...... the CO2 concentration for a given pCO2
Moreover; the lower the saturation of Hb with O2, the larger the CO2 concentration for a given pCO2
254
How does an increase in SO2 influence the CO2 curve?
Right shifted
255
Does the lung or the kidney excrete the most acids?
The lung excretes over 10 000 mEq of carbonic acid per day, compared with less than 100 mEq of fixed acids by the kidney. Therefore; by altering alveolar ventilation and thus the elimination of CO2; the body has great control over its acid-base balance.
256
What is the pH resulting from?
From the solution of CO2 in blood and the consequent dissociation of carbonic acid is given by the Henderson-Hasselbaclch equation.
H2CO3 ---H+ ? HCO3-
257
As long as the ratio of bicarbonate conc to (PCO2 x 0.03) remains equal to ....., the pH will remain at 7,4.
20
258
Which organ determines briefly the bicarbonate concentration
The kidney
259
Which organ determines briefly the PCO2 concentration
The lung
260
How does an increase in bicarbonate conc displace the buffer line on the Davenport diagram?
Displaces the buffer line upward (base excess i Fig 6-8)
261
How does a reduced bicarbonate conc displace the buffer line on the Davenport diagram?
Displaces the buffer line downward. (negative base excess/baase deficit in the ex i Fig 6-8)
262
What causes a respiratory acidosis?
An increase in PCO2: which reduced the HCO3-/PCO2 ratio and thus depresses the pH.
263
Whenever the PCO2 rises, the bicarbonate......to some extent
Whenever the PCO2 rises, the bicarbonate must also increase to some extent because of dissociation of the carbonic acid produced. However, the ratio of HCO3-/PCO2 falls.
264
Causes of CO2 retention?
Hypoventilation or ventilation-perfusion inequality.
265
If the respiratory acidosis persists; how does the kidney respond?
By conserving HCO3-. It is prompted to do this by the increased PCO2 in the renal tubular cells, which then excrete a more acid urine by secreting H+ ions.
266
In which form are H+ ions secreted from the kidney in case of respiratory acidosis?
Excreted as H2PO4- or NH4-. The HCO3- are reabsorbed. The resulting increase in plasma HCO3- then moves the HCO3-/PCO2 ratio back up toward its normal level (= compensated respiratory acidosis). The renal compensation is typically not complete, and so the pH does not fully return to its normal level of 7.4.
267
How can the extent of renal compensation for resp acidosis be determined?
From the base excess; that is the vertical distance between the buffer lines BA and DE. (Fig 6-8)
268
What causes a respiratory alkalosis?
Caused by a decrease in PCO2; which increases the HCO3-/PCO2 ratio; and thus elevates the pH.
269
What causes a decrease in PCO2?
Hyperventilation, for ex at high altitude.
270
Compensation for respiratory alkalosis?
Renal compensation occurs by an increased excretion of bicarbonate, thus returning the HCO3-/PCO2 ratio back toward normal. After a prolonged stay at high altitude, the renal compensation may be nearly complete. There is a negative base excess or base deficit.
271
Primary problem if a patient has respiratory acidosis? Compensation?
Increased pCO2. Compensation: Increased HCO3-
272
Primary problem if a patient has metabolic acidosis? Compensation?
Decreased HCO3-. Compensation: Decreased PCO2
273
Primary problem if a patient has respiratory alkalosis? Compensation?
Decreased PCO2. Compensation: Decreased HCO3-
274
Primary problem if a patient has metabolic alkalosis? Compensation?
Increased HCO3-. Compensation: Often none
275
What does "metabolic" means?
A primary change in HCO3-
276
What happens in scenarios of metabolic acidosis?
The ratio of HCO3- to PCO2 falls, thus depressing the pH.
277
Examples of etiologies for a lowered HCO3- in cases of metabolic acidosis?
Accumulation of acids in the blood, as in uncontrolled diabetes mellitus.
After tissue hypoxia; which releases lactic acid
278
Compensations for an lowered HCO3- (metabolic acidosis)
Increase in ventilation that lowers the PCO2 and raises the depressed HCO3-/PCO2 ratio.
279
Chiefly action of raised ventilation in cases of metabolic acidosis?
Chiefly the action of H+ ions on the peripheral chemoreceptors.
280
Metabolic alkalosis; why?
Increase in HCO3- raises the HCO3-/PCO2 ratio and thus the pH.
281
Why metabolic alkalosis?
Excessive ingestion of alkalis, and loss of acid gastric secretion by vomiting are causes.
282
Compensation for metabolic acidosis?
Resp compensation: But often small and may be absent. Base excess os increased
283
Mixed resp and metabolic disturbances may occur. Easy to unravel the sequence of events?
No, Often difficult.
284
How does O2 and CO2 move between the systemic capillary blood and the tissue cells, and also between the capillary blood and alveolar gas in the lung?
By simple diffusion
285
Thickness of blood-gas barrier?
Less than 0,5 um. But the distance between open capillaries in resting muscle is on the order of 50 um
286
Mechanism during exercise, when the O2 consumption of the muscle increases?
Additional capillaries open up, thus reducing the diffusion distance and increasing the the area for diffusion.
287
During exercise; is CO2 or O2 the most problematic?
Because CO2 diffuses about 20 times faster than O2 through tissue, elimination of CO2 is much less of a problem than is O2 delivery
288
If anaerobe metabolism (utilizing O2) is impossible: what can occur under these conditions?
The tissue may turn to anaerobic glycolysis with the formation of lactic acid.
289
Hypoxia
Abnormally low PO2 in tissues. Frequently caused by low O2 delivery, which can be expressed as the cardiac output multiplied by the arterial O2 concentration. (or Q x CaO2)
290
Why can tissue hypoxia occur? (3 different main mechanisms, and 1 extra fourth)
1) A low PO2 in arterial blood caused, for example, by pulmonary disease (Hypoxic hypoxia)
2) A reduced ability of blood to carry O2 as in anemia or carbon monoxide poisoning (anemic hypoxia)
3) A reduction in tissue blood flow, either generalized, as in chock, or because of local obstruction (circulatory hypoxia)
4) Some toxic substances (for ex cyanide) that interferes with the ability of the tissues to utilize available O2 (histotoxic hypoxia)
291
The PO2 in some tissues is less than 5 mmHg, and the purpose of the much higher PO2 in the capillary blood is to.....?
To provide an adequate gradient for diffusion.
292
Factors determining the O2 delivery to tissue include?
The blood O2 concentration and the blood flow.
293
A patient with severe anemia has normal lungs. You would expect?
Low oxygen conc in mixed venous blood. The oxygen conc of arterial blood will be reduced, and therefore, if cardiac output and oxygen uptake are normal, the oxygen concentration of mixed venous blood will also be reduced.
294
Most important muscle of inspiration? Which nerve supply this muscle?
The diaphragm. The phrenic nerve
295
Is inspiration active?
Yes
296
Is expiration active?
passive during rest/quiet breathing.
297
Describe inspiration
On inspiration, the dome-shaped diaphragm contracts, the abdominal contents are forced down and forward, and the rib cage is widened. Both increase the volume of the thorax.
298
Describe forced expiration
On forced expiration, the abdominal muscles contract and push the diaphragm up
299
What happens when the external intercostal muscles contract?
The internal intercostals?
The ribs are pulled upward and forward, and they rotate on an axis joining the tubercle and the head of a rib. As a result, both the lateral and anteroposterior diameters of the thorax increase (inspiration)
The internal intercostals have the opposite action (expiration).
300
Other muscles (than the diaphragm, internal/external intercostals) that are respiratory muscles?
abdominal muscles and accessory muscles
301
What is hysteresis behavior?
The curves that the lung follows during inflation and deflation are different. This behavior is known as hysteresis.
302
When is the lung volume the largest? During inflation or deflation?
During deflation
303
What is a transpulmonary pressure?
The difference between the inside and the outside of the lung
304
Is the pressure inside the airways and alveoli of the lung the same as atmospheric pressure?
Yes
305
What is compliance?
The slope of the pressure-volume curve, or the volume change per unit pressure change. In the normal range, the lung is remarkably distensible or very compliant. However, at high expanding pressures, the lung is stiffer, and its compliance is smaller (as shown by a flatter slope of the pressure-volume curve)
306
What can cause a reduced compliance? (4)
1. Increase of fibrous tissue in the lung (plum fibrosis).
2. Alveolar edema (prevents inflation of some alveoli)
3. If the lung remains unventilated for a lund period, especially if its volume is low (this may be partly caused by atelectasis (collapse) of some units, but increases in surface tension also occur.
4. If the pulmonary venous pressure is increased and the lung becomes engorged with blood.
307
What can cause an increased compliance? (3)
1. Pulmonary emphysema
2. Normal aging lung
(in both instances, an alteration in the elastic tissue in the lung
3. Asthma attack
308
Is the compliance of the lung dependent on its size?
Yes. The change in volume per unit change of pressure will be larger for a human lung than a mouse lung.
309
Is the pressure surrounding the lung the same as the atmospheric pressure?
No, it is less than atmospheric pressure because of the elastic recoils of the lung.
310
What is responsible for the lung´s elastic behavior, that is the tendency to return to its resting volume after distension?
Elastic tissue (elastin and collagen fibers): the changes in elastic recoil that occurs in the lung with age and in emphysema are presumably caused by changes in this elastic tissue.
311
Is the pressure-volume curve of the lung linear or nonlinear?
Nonlinear, with the lung becoming stiffer at high volumes
312
The behavior of the pressure-volume curve of the lung depend on structural proteins (collagen, elastin), but also on......?
The surface tension (liquid film lining the alveoli)
313
What is the surface tension?
The force (in dynes, for example) acting across an imaginary line 1 cm long in a liquid surface.
314
If comparing pressure-volume curves of air-filled and saline-filled lungs; which lung has the higher compliance and also much less hysteresis?
The saline-filled lungs.
315
Some of the cells lining the alveoli secrete a material that profoundly lowers the surface tension of the alveolar lining fluid. Which material?
Surfactant.
316
What is surfactant?
A phospholipid, and dipalmitoyl phosphatidylcholine (DPPC) is an important constituent. Formed relatively late in fetal life.
317
What is phospholipid DPPC synthesized from?
Produced by type II alveolar epithelial cell. Synthesized in the lung from fatty acids that are either extracted from the blood or are themselves synthesized in the lung. Synthesis is fast, and there is a rapid turnover of surfactant.
318
How does surfactant reduce the surface tension so much?
Apparently, the molecules of DPPC are hydrophobic at one end and hydrophilic at the other, and they align themselves in the surface. When this occurs, their intermolecular repulsive forces oppose the normal attracting forces between the liquid surface molecules that are responsible for surface tension. The reduction in surface tension is greater when the film is compressed because the molecules of DPPC are then crowded closer together and repel each other more.
319
Physical advantages of surfactant?
1. A low surface tension in the alveoli increases the compliance of the lung and reduced the work of expanding it with each breath.
2. Stability of the alveoli is promoted (decreased risk of atelectasis (collapse) in the 500 million alveoli). the pressure generated by an given surface force in a bubble is inversely proportional to its radius, with the result that if the surface tensions are the same, the pressure inside a small bubble exceeds that in a large bubble. However, when the lung washings are present, a small surface area is associated with a small surface tension. Thus, the tendency for small alveoli to empty into large alveoli is apparently reduced.
3. Help to keep the alveoli dry. Just as the surface tension forces tend to collapse alveoli, they also tend to suck fluid out of the capillaries. In effect, the surface tension of the curved alveolar surface reduced the hydrostatic pressure in the tissue outside the capillaries.. By reducing these surface forces, surfactant prevents the transudation of fluid.
320
Consequences of loss of surfactant?
Stiff lungs (low compliance)
Areas of atelectasis
Alveoli filled with transudate (pulmonary edema)
321
Another mechanism that contributes to the stability of the alveoli in the lung?
Alveoli are surrounded by other alveoli and are therefore supported by one another (interdependence).
322
Why is the intrapleural pressure less negative at the base of the lung than at the apex?
Because of the weight of the lung.
As a consequence, the basal lung is relatively compressed in its resting state but expands more on inspiration than the apex.
323
Situation at vey low lung volumes: Intrapleural pressures are less negative, and the pressure at the base actually exceeds airway (atmospheric) pressure. What are the consequences?
As a consequence, airway closure occurs in this region, and no gas enters with small inspiration.
324
The tendency of the lung to recoil to its deflated volume is balanced by the tendency of.........
......the tendency of the chest cage to bow out. As a result, the intrapleural pressure is subatmospheric. Pneumothorax allows the lung to collapse and the thorax to spring out.
325
Elastic properties of both the ....and the.... determines their combined volume
the lung and the chest wall
326
When and where can airway closure occur in healthy people?
The compressed region of the lung at the base does not have all its gas squeeed out. In practice, small airways , probably in the region of respiratory bronchioles close first, thus tarpapering gas in the distal alveoli. This airway closure occurs only at very low lung volumes in young normal subjects. However, in elderly apparently normal people, airway closure in the lowermost regions of the lung occurs at higher volumes and may be present at functional residual capacity (FRC). The reason is that the aging lung loses some of its elastic recoil, and intrapleural pressures therefore become less negative. A similar situation frequently develops in patients with some types of chronic lung disease.
327
At FRC, the inward pull of the lung is balanced by the outward spring of....
.....of the chest wall
328
Chest wall tends to expand at volumes up to about..... of vital capacity
75%
329
A difference of pressure exists between the ends of a tube if air flows through it. The pressure difference depends on the rate and the pattern of flow (like if it goes through straight circular tubes). What is laminar flow?
At low flow, the stream lines are parallel to the sides of the tube.
330
Turbulence?
As the flow rate is increased, unsteadiness develops, especially at branches. Here, separation of the stream lines from the wall may occur with the formation of local eddies. At still higher flow rates, complete disorganization of the stream lines is seen.
331
Which factors are involved in the calculation of laminar flow in a straight circular tube?
Driving pressure (P)
Radius (R)
Viscosity (n)
length (l)
Driving pressure is proportional to flow rate
Flow resistance is driving pressure divided by flow
332
The tube radius is important for the pressure-flow relationship in the laminar flow profile: What happens if the radius is halved? If the length is doubled?
The resistance increases 16-fold if the tube radius is halved.
The resistance is only doubled if the length is doubled.
333
Does both viscosity of the gas as well as density affect pressure-flow relationship under laminar flow conditions?
No, only viscosity.
334
Any differences in airway resistance for gas that moves in the center of the tube compared to the "average" gas in the laminar flow?
The gas in the center of the tube moves twice as fast as the average velocity. (changing velocity profile)
335
Turbulent flow has different properties from that of the laminar flow. Which?
Here, pressure is not proportional to flow rate, but approximately to its square: P= KV2. In addition, the viscosity of the gas becomes relatively unimportant, but an increase in gas density increases the pressure drop for a given flow.
Turbulent flow does not have the high axial flow velocity that is characteristic of laminar flow.
336
Whether flow will be laminar of turbulent depends to a large extent on .......number
the Reynolds number (Re). Re= 2rvd/n
d=density
v=average velocity
r= radius
n= viscosity
337
In the rapidly branching system such as the lung, fully developed laminar flow probably only occurs in.....
...in the very small airways where the Reynolds number are very low. In most of the bronchial tree, flow is transitional, whereas true turbulence may occur in the trachea, especially on exercise when flow velocities are high.
In general, driving pressure is determined by both the flow rate and its square.
338
In laminar flow, resistance is inversely proportional to.....
...to the fourth power of the radius of the tube
339
Turbulent flow is most likely to occur at .....Reynolds number, that is when inertial forces dominate over the viscous forces
high Reynolds numbers.
340
What is airway resistance?
The pressure difference between the alveoli and the mouth divided by a flow rate
341
Why does intrapleural pressure fall during inspiration? (2)
1: As the lung expands, its elastic recoil increases.
| 2. The reduction in alveolar pressure causes a further fall in intrapleural pressure.
342
What happens with intrapleural pressure during expiration?
Intrapleural pressure is less negative than it would be in the absence of airway resistance because alveolar pressure is positive. Indeed, with a forced expiration, intrapleural pressure goes above zero.
343
Where in the airways is the major site of resistance?
In the medium-sized bronchi. (The very small bronchioles contribute relatively little resistance: because the peripheral airways contribute so little resistance, it is probable that considerable small airway disease can be present before the usual measurements of airway resistance can detect an abnormality.
344
What happens with the airway resistance if lung volume is reduced?
Airway resistance rises rapidly. At very low lung volumes, the small airways may close completely, especially at the bottom of the lung, where the lung is less well expanded.
345
Breathing pattern of some patients who have increased airway resistance?
Some breathe at high lung volumes; this helps to reduce their airway resistance
346
What happens if the bronchial smooth muscle contracts?
It narrows the airways and increases airway resistance.
347
How can contraction of the bronchial smooth muscles occur? Which nerve (motor innovation)
This may occur reflexly through the stimulation of receptors in the trachea and large bronchi by irritants such as cigarette smoke. Motor innervation is by the vagus nerve.
348
The tone of the smooth muscle is under control of the autonomic nerve system. Stimulation of adrenergic receptors causes...?
Bronchodilatation
349
The tone of the smooth muscle is under control of the autonomic nerve system. Stimulation of adrenergic receptors causes bronchodilatation. Which medicines can stimulate to bronchodilatation
Epinephrine and isoproterenol
350
Beta 1 receptors occur principally in....
...in the heart
351
Main effects of beta 2 receptors?
Relaxes smooth muscle in the bronchi, blood vessels and uterus
352
Selective B2 adrenergic agonists can be used extensively in the treatment of...?
Asthma
353
Parasympathetic activity effect on the bronchi?
Bronchiconstriction
354
Acethylcholine effect on the bronchi?
Bronchiconstriction
355
How does a fall of PCO2 in alveolar gas influence the airways?
Causes an increase in airway resistance, apparently as a result of a direct action on bronchiolar smooth muscle
356
Histamine effect if injected into the pulmonary artery?
Causes constriction of smooth muscles located in the alveolar ducts
357
Do density or viscosity have the most influence (increased resistance) on resistance in the airways?
Density the most. Breathing a dense gas, as when diving, increases resistance.
358
Why does the airway resistance decrease at the lung volume rises?
Because the airways are then pulled open
359
Effect of a dynamic compression of airways?
Limits air flow in normal subjects during a forced expiration
360
Dynamic compression of airways may occur in diseased lungs at relatively low expiratory flow rates; thus........
...thus reducing exercise ability
361
How is flow during dynamic compression determined?
Flow is determined by alveolar pressure minus pleural pressure (not mouth pressure) and is therefore independent of effort
362
Dynamic compression of airways is exaggerated in some lung diseases. Why?
By reduced lung elastic recoil and loss of radial traction on airways
363
Effect on intrapleural and alveolar pressure by forced expiration?
Both intrapleural and alveolar pressure increase.
364
How does maximal flow influence lung volumes?
| 7-16
Lung volumes decreases because of the difference between alveolar and intrapleural pressure decreases and the airways become narrower.
365
Resistance of airways when lung volumes fall?
Rises. Therefore, the pressure within the airways falls more rapidly with distance from the alveoli
366
2 things that can exaggerate the flow-limiting mechanism?
1. Any increase in resistance of the peripheral airways (because that magnifies the pressure drop along them and thus decreases the intrabronchial pressure during expiration).
2. Low lung volume (because that reduced the driving pressure. This driving pressure is also reduced if recoil is reduced as in emphysema.)
367
Causes of regional differences in ventilation in the lung?
1. Topographical differences
2. Compliance of the lung units. The shorter the time available for inspiration (fast breathing rate), the smaller the inspired volume. Thus, inequality of ventilation can result from alterations in either local distensibility or airway resistance, and the pattern of inequality will depend on the frequency of breathing.
3. Incomplete diffusion within the airways of the respiratory zone. Normally the dominant mechanism of ventilation of the lung beyond the terminal bronchioles is diffusion. If there is dilation of the airways in the region of the respiratory bronchioles, as in some diseases, the distance to be covered by diffusion may be enormously increased = uneven ventilation along the lung unit.
368
What is pulmonary resistance?
the total resistance (distinguish from airway resistance) required to overcome the viscous forces within tissues as they slide over each other when the lung and chest wall are moved.
369
Work of breathing
Pressure x volume.
- During inspiration: The inspiratory work done to overcome the elastic forces and viscous forces.
- During expiration: Work required to overcome airway (+tissue) resistance.
370
In laminar flow as exists in small airways, the resistance is inversely proportional to the ....
...to the fourth power of the radius
371
If airway smooth muscle is contracted, as in asthma, the resistance is reduced by for example .....(medicine)
Beta-2 adrenergic agonists.
372
Dynamic compression of the airways during a forced expiration results in flow that is effort-independent. The driving force is then....
The driving force is then alveolar minus intrapleural pressure. In patients with chronic obstructive lung disease, dynamic compression can occur during mild exercise, thus causing severe disability.
373
Concerning contraction of the diaphragm; It tends to.....the diaphragm
To flatten.
374
Compliance....with age
increases
375
Filling an animal lung ith saline .....compliance
increases
376
Removing a lobe reduced total pulmonary compliance. Why
if there is less lung, the global change in volume per unit change in pressure will be reduced.
377
Absence of surfactant.....compliance?
Decreases
378
In the upright lung at FRC, inspiration causes larger......in volume of the alveolar at the base of the lung compared with those near the apex (fig 7-8)
larger increase.
379
Correct or not? during resting conditions: The flow velocity of gas in the large airways exceeds that in the terminal bronchioles during expiration
correct
380
At expiration during normal resting conditions, alveolar pressure is associated with an alveolar pressure that......... atmospheric pressure.
exceeds
381
If a normal subject develops a spontaneous pneumothorax of the right lung, you would expect?
The right lung to contract,the chest wall on the right to expand, the diaphragm on the right to move down, the mediastinum to shift to the left, and the blood flow to the rift lung will be reduced both because its volume is small and also there is hypoxic pulmonary vasoconstriction.
382
According to Pouiseuille's law, reducing the radius of an airway to one-third will increase its resistance how many fold?
81. Pouiseuilles law states that during laminar flow, airway resistance is inversely proportional to the 4th power of the radius, other things being equal. Therefore, a reduction in the radius by a factor of 3 increases the resistance by 3 upphöjd i 4 = 81
383
Is flow more likely to be turbulent in small airways than in the trachea?
No. Flow is more likely to be turbulent in large airways.
384
The lower viscosity, the less likely is turbulent to occur?
No, the higher the viscosity, the less likely is turbulence to occur
385
In pure laminar flow, halving the radius of the airways increases its resistance eight folds. True or false?
False. Should be increases its resistance 16-fold.
386
Going to high altitude decreases the resistance of the airways. Why?
The density of the air is reduced.
387
A normal subject makes an inspiratory effort against a closed airway. You would expect the following to occur: Pressure inside the pulmonary capillaries falls. The internal muscles become active. Intrapleural pressure increases (becomes less negative). Alveolar pressure falls more than intrapleural pressure. Tension in the diaphragm decreases.
Correct: Pressure inside the pulmonary capillaries (an inside the rest of the thorax) falls.
Other alternatives are incorrect. Tension in the diaphragm increases, external, not internal intercostal muscles become active, intrapleural pressure becomes more negative, and alveolar pressure will fall equally with intrapleural pressure if lung volume does not change.
If lung volume does increase slightly, intrapleural pressure will fall more than alveolar pressure.
388
3 basic elements of the respiratory control system?
1. Sensors (chemoreceptors) that gather information and feed it to the....
2. ....the central controller in the brain, which coordinates the information and, in turn, sends impulses to the....
3. ....the effectors (respiratory muscles), which cause ventilation
389
The normal autonomic process of breathing originates in impulses that come from the .......
the brainstem.
390
Which area in the brain can override the centers in the brainstem if voluntary control of breathing is desired?
The cortex. Additional input from other parts of the brain (such as the limbic system and hypothalamus) occurs under certain conditions (such as in emotional states such as rage and fear)
391
Three main groups of neurons are recognized in the brainstem that control the rhythmic pattern of inspiration and expiration.
Located in the medulla and pons:
1. Medullary respiratory center in the reticular formation of the medulla beneath the floor of the fourth ventricle (responsible for the basic rhythm of ventilation)
2. Apneustic center in the lower pons
3. Pneumotaxic center in the upper pons (fine tuning of respire rhythm)
392
Is the expiratory area in the medulla active during normal quit breathing?
No, the expiratory area is quiescent during normal quiet breathing because ventilation is the achieved by active contraction of inspiratory muscles (chiefly the diaphragm) followed by passive relaxation of the chest wall to its equilibrium position. However, in more forceful breathing, for example, on exercise, expiration becomes active as a result of the activity of the expiratory cells.
393
Role of the pneumotaxic center in the upper pons?
This area appears to "switch off" or inhibit inspiration and thus regulate inspiration volume and, secondarily, respiratory rate. "Fine tuning" of resp rhythm (a normal rhythm can exist in the absence of this center).
394
The respiratory centers receive input from the.....
.....from the chemoreceptors, lung and other receptors, and the cortex.
395
Major output (nerve) from the respiratory centers is the....
The phrenic nerves. But there are also impulses to other respiratory muscles.
396
Breathing is under voluntary control to a considerable extent. Which area in the brain can override the function of the brainstem within limits.
The cortex can override the function of the brainstem within limits. Voluntary hyperventilation (consequent alkalosis can be a result) or hypoventilation can occur.
397
Voluntary hypoventilation is limited by?
For example arterial PCO2 and PO2. A preliminary period of hyperventilation increases breath-holding time, especially if oxygen is breathed.
398
Muscles of respiration include?
The diaphragm, intercostal muscles, abdominal muscles and accessory muscles. Important that these "effectors" works in a coordinated manner (this is the responsibility of the central controller)
399
What is a chemoreceptor?
A receptor that responds to a change in the chemical composition of the blood or other fluid around it.
400
Where are the most important central chemoreceptors important for respiration located?
Located near the ventral surface of the medulla
401
Are the central chemorecpetors sensitive to both PCO2 and PO2 of blood?
No, sensitive to PCO2, but not PO2 of blood.
402
Central chemoreceptors respond to the change in pH of the......?
Central chemoreceptors respond to the change in pH of the ECF/CSF when CO2 diffuses out of the cerebral capillaries.
403
How does local application of H+ or dissolved CO2 to the area of the central chemoreceptors in the medulla affect breathing?
Stimulates breathing within a few seconds
404
How does a decrease in H+ concentration to the area of the central chemoreceptors in the medulla affect breathing?
Inhibits it.
405
The composition of the extracellular fluid around the receptors is governed by the?
By the cerebrospinal fluid (CSF), local blood flow, and local metabolism, of which the CSF is the most important.
406
How is the permeability of the blood-brain barrier to H+, HCO3- ions and CO2?
Relatively impermeable to H+ and HCO3-ions, but molecular CO2 can diffuse across it easily.
407
How can CO2 level in blood regulate ventilation?
When the blood PCO2 rises, CO2 diffuses into the CSF from the cerebral blood vessels, liberating H+ ions that stimulate the chemoreceptors. Thus, the CO2 level in blood regulates ventilation chiefly by its effect on the pH of the CSF. The resulting hyperventilation reduces the PCO2 in the blood and therefore in the CSF. The cerebral vasodilation that accompanies an increased arterial PCO2 enhances diffusion of CO2 into the CSF and the brain extracellular fluid.
408
Normal pH of the CSF?
7,32. Because the CSF contains much less protein than blood, it has a much lower buffering capacity. As a result, the change in CSF pH for a given change in PCO2 is peter than in blood. If the CSF pH is displaced over a prolonged period, a compensatory change in HCO3- occurs as a result of transport across the blood-brain barrier.
409
Is the change in pH in CSF quicker or more slowly compared to pH of arterial blood by renal compensation.
Quicker in the CSF compared to blood pH: accordingly; CSF pH has a more important effect on changes in the level of ventilation and the arterial pCO2
410
Where are the peripheral receptors located?
In the carotid bodies at the bifurcation of the common carotid arteries, and in the aortic bodies and below the aortic arch.
411
What does the peripheral chemoreceptors respond to?
To decreased arterial PO2 and pH, and increased arterial PCO2 and H+.
These receptors respond rapidly to arterial rather than to venous pO2. Responsible for the increase of ventilation that occurs in response to arterial hypoxemia.
(in the absence of these receptors, severe hypoxemia may depress ventilation), presumably through a direct effect on the respiratory centers.
412
Is the response of the peripheral chemoreceptors to arterial pCO2 more important than that of the central chemoreceptors.
No, less important. But more rapid (of value in particular situations of abrupt changes in pCO2. The response is magnified if the arterial PO2 is lowered
413
Increases in chemoreceptor activity in response to decreases in arterial PO2 are potentiated by....?
Increases in arterial PCO2, and in th the carotid bodies; by decreases in pH.
414
Lung receptors (4 types)?
1. pulmonary stretch receptors
2. Irritant receptors
3. J receptors
4. Bronchial C fibers
415
Other receptors affecting the respiratory function?
1. Nose and upper airway receptor
2. Joint and muscle receptors
3. Gamma system
4. Arterial baroreceptors
5. Pain and temperature (stimulation of many afferent nerves). Pain often causes a period of apnea followed by hyperventilation.
416
How can an increase resp. decrease in arterial blood pressure influence the ventilation?
Increased arterial blood pressure: Reflex hypoventilation or apnea through stimulation of the aortic and carotid sinus baroreceptors.
Decreased arterial blood pressure: May result in hyperventilation
417
What is the most important stimulus to ventilation under most conditions?
Arterial PCO2 (tightly controlled)
418
A reduction in arterial PCO2 is very effective in......the stimulus to ventilation
reducing
419
Ventilatory response to hypoxia: Are both the central and the peripheral chemoreceptors involved?
No, only the peripheral
420
Ventilatory response to hypoxia: When is the control particularly important?
At high altitude and in long-term hypoxemia.
421
Reduction of PO2 in arterial blood stimulates ventilation. Is the role of this hypoxic stimulus important?
PO2 can normally be reduced far without evoking a ventilatory response: accordingly; the role of this hypoxic stimulus in the day-to-day control of ventilation is small. However, on ascent to high altitude, a large increase in ventilation occurs in response to the hypoxia.
422
In some patients with severe lung disease, the hypoxic drive to ventilation becomes very important. Why?
These patients have chronic CO2 retention, and the pH of their brain extracellular fluid has returned to near normal in spite of a raised PCO2 (lost most of their increase in the stimulus to ventilation from CO2). In addition, the initial depression of blood pH has been nearly abolished by renal compensation, so there is little pH stimulation of the peripheral chemoreceptors. Under these stimulus, the arterial hypoxemia becomes the chief stimulus to ventilation. If such a patient is given a high O2 mixture to breathe to relieve the hypoxemia, ventilation may become
grossly depressed. The ventilatory state is best monitored by measuring arterial PCO2.
423
Hypoxemia reflexly stimulates ventilation by its action on the carotid and aortic body chemoreceptors. It has no action on the central chemoreceptores. However, prolonged hypoxemia can cause mild cerebra acidosis, which in turn....
...stimulates ventilation
424
A reduction in arterial blood pH .....ventilation
stimulates. Often difficult to separate from the ventilatory response resulting from that caused by an accompanying rise in pCO2.
425
Chief site of action of a reduced arterial pH?
```
peripheral chemoreceptors (central chemoreceptors or the
respiratory center itself if large enough. In this case, the blood -brain barrier becomes partly permeable to H+ ions
```
426
Cheyne-stokes respiration?
Characterized by periods of apnea of 10 to 20 seconds, separated by approximately equal periods of hyperventilation when the tidal volume gradually waxes and the wanes. This pattern is frequently seen at high altitude, especially at night during sleep. It is also found in some patients with severe heart disease or brain damage.
427
The peripheral chemoreceptors, chiefly in the carotid bodies, respond to ....?
a reduced PO2 and increases in PCO2 and H+ concentration. The response to increased CO2 is less marked than that from the central chemoreceptors but occurs more rapidly.
428
The.....of the blood is the most important factor controlling ventilation under normal conditions, and most of the control is via the central chemoreceptors.
CO2
429
Does PO2 of the blood normally affect ventilation?
No, not normally, but it becomes important at high altitude and is some patients with lung disease.
430
Wat does the increase in respiratory exchange ratio on exercise reflect?
A greater reliance on carbohydrate rather than fat to produce the required energy. During severe exercise, lactic acid is produce by anaerobic glycolysis, and additional CO2 is is therefore eliminated from bicarbonate. In addition, there is increased CO2 elimination because the increased H+ concentration stimulates the peripheral chemoreceptors, thus increasing ventilation.
431
Ventilation initially increases linearity with O2 consumption but what happens when substantial amounts of blood lactate are formed?
O2 consumption rised more rapidly.
432
How is the increase in cardiac output during exercise compare to ventilation?
Cardiac output increases more slowly and is only about a quarter of the increase in ventilation. This makes sense because it is much easier to move air than to move blood.
433
The increase in cardiac output is associated with elevations of which pulmonary pressures (arterial or venous? both?)
The increase in cardiac output is associated with elevations of both pulmonary arterial and pulmonary venous pressures, which accounts for the recruitment and distnesion of pulmonary capillaries.
434
What happens with pulmonary vascular resistance when cardiac output increases during exercise?
Pulmonary vascular resistance falls
435
What happens with the oxygen dissociation curve during exercise?
Moves to the right in exercising muscles because of the increase in PCO2, H+ conc and temperature. This assists in the unloading of oxygen to the muscles. When the blood returns to the lung, the temperature of the blood falls a little, and the curve shifts leftward somewhat.
436
Why does the hematokrit increase on exercise in dogs (and horses)?
Because red cells are ejected from the spleen, but this does not occur in humans.
437
What happens with capillaries in peripheral tissues during exercise?
Additional capillaries open up, thus reducing the diffusion path length to the mitochondria.
438
Why does the peripheral vascular resistance fall during exercise?
Because the large increase in cardiac output is not associated with much of an increase in mean arterial pressure (at least not during dynamic exercise). During static exercise, large increases in systemic arterial pressure often occur. Exercise training increases the numer of capillaries and mitochondria in skeletal muscles
439
Increase in ventilation occurs during exercise. The net result is that the arterial PO2 , PCO2 and pH are little affected by moderate exercise. What about during high work?
PCO2 often falls, PO2 rises and pH falls because of lactic acidosis
440
The most important feature of acclimatization to high altitude? (hypoxia)
Hyperventilation thereby reducing the PCO2 and increasing the alveolar PO2. The mechanism of the hyperventilation is hypoxic stimulation of the peripheral chemoreceptors. The resulting low arterial PCO2 and alkalosis tend to inhibit this increase in ventilation, but after a day or to, the cerebrospinal fluid (CSF) pH is brought partly back by movement of bicarbonate out of the CSF. These brakes on ventilation are then reduced, and it increases further.
(people who are born at high altitude have a diminished ventilatory response)
441
Another valuable feature of acclimatization to high altitude besides ventilation?
Increase in the red blood cell concentration of the blood (slow to develop and of minor value). The resulting rise in hemoglobin concentration, and therefore O2 carrying capacity, means that although the arterial PO2 and O2 saturation are diminished, the O2 concentration of the arterial blood may be normal or even above normal. The polycythemia also tends to maintain the PO2 of mixed venous blood. Unfortunately, although the polycythemia of high altitude increases the O2 carrying capacity of the blood, it also raises the blood viscosity (which can be deleterious).
442
What is the stimulus for the increased production of red blood cells?
Hypoxemia, which releases erythropoietin from the kidney, which in turn stimulates the bone marrow.
Polycythemia is also seen in many patients with chronic hypoxemia caused by lung or heart disease.
443
Other physiologic changes at high altitude?
Increases in cellular oxidative enzymes and the concentration of capillaries in some tissues. Pulmonary vasoconstriction occurs in response to alveolar hypoxia.
444
Rightward or leftward shift of the O2 dissociation curve at moderate altitudes?
Rightward shift: resulting in a better unloading of O2 in venous blood at a given PO2. This is due to an increase in concentration of 2,3-DPG which develops primarily because of the respiratory alkalosis.
445
Rightward or leftward shift of the O2 dissociation curve at higher altitudes?
Leftward shift caused by the resp alkalosis, and this assist in the loading of O2 in the pulmonary capillaries. The number of capillaries per unit volume in peripheral tissues increases, and chafes occur in the oxidative enzymes inside the cells.
446
Response of the pulmonary vessels at high altitude?
Pulmonary vasoconstriction in response to alveolar hypoxia. This increases the pulmonary arterial pressure and the work done by the right heart. The hypertension is exaggerated by the polycythemia, which raises the viscosity of the blood. Hypertrophy of the right heart is seen, with characteristic changes in the electrocardiogram. Pulmonary hypertension is sometimes associated with pulmonary edema, although the pulmonary venous pressure is normal. The probable mechanism is that the arterial vasoconstriction is uneven, an leakage occurs in unprotected, damaged capillaries. The edema fluid has a high protein concentration, indicating that the permeability of the capillaries is increased.
447
Why does acute mountain sickness occur?
Due to hypoxemia and alkalosis
448
What can occur if high concentrations of 02 are breathed for many hours?
Damage to the lung may occur. Like pulmonary edema. First pathological changes seen in the endothelial cells of the pulmonary capillaries. (Also risk for blindness in premature infants because of fibrous tissue formation behind the lens).
449
Common postoperative problem in patients treated with high O2 mixtures?
Postoperative atelectasis of alveoli beyond blocked (for example by mucus). airways. Collapse is particularly likely to occur at the bottom of the lung, where the parenchyma is least well expanded. This can occur when the sum of the gas partial pressures in the mixed venous blood is less than in the alveoli
450
In severe CO poisoning the hemoglobin is bound to CO and is therefore unavailable to carry O2. Potential treatment?
By raising the inspired PO2, the amount of dissolved O2 in arterial blood can be increases, and thus the needs of the tissues can be met without functioning hemoglobin. Occasionally, an anemic crisis is managed this way.
451
Potential problems if inhaling too much nitrogen oxides?
Can cause inflammation of the upper respiratory tract and eye irritations.
452
Where does gas exchange take place during fetal life?
Through the placenta. Its circulation is in parallel with that of the peripheral tissues of the fetus, unlike the situation in the adult, in which the pulmonary circulation is in series with the systemic circulation.
453
Maternal blood enters the placenta from the ........
...from the uterine arteries, and surges into small spaces called intervillous sinusoids that function like the alveoli in the adult.
454
Fetal blood from the aorta is supplied to capillary loops that protrude into.......
.....that protrude into the intervillous spaces. gas exchange occurs across the blood-blood barrier. Gas exchange in fetal life not a very effective system for gas exchange compared to in adults.
455
Fetal blood mixes with venous blood draining from the fetal tissues and reaches the........via the infers vena cava.
reaches the right atrium. Most of this blood flows directly into the left atrium through the open foramen oval (FO) and this is distributed via the ascending aorta to the brain and heart. Less-well-oxygenated blood returning to the RA via the superior vena cava finds its way to the right ventricle. but only a small portion reaches the lungs. Most is shunt to the aorta through the ductus arterioles.
456
What is the ner result of the complex fetal blood arrangement?
The best-oxygenated blood reaches the brain and heart, and the non-gas-exchanging lungs receive only about 15% of the cardiac output.
457
3 most important differences between the fetal and adult circulations?
1. The placenta is i parallel with the circulation to the tissues, whereas the lung is in series in the adult.
2. The DA shunts most of the blood from the pulmonary artery to the descending aorta.
3. Streaming within the right atrium means that the oxygenated blood from the placenta is preferentially delivered to the LA throughout the foramen oval and therefore via the ascending aorta to the brain.
458
Babies makes strong inspiratory efforts and takes its first breaths. What happens?
The baby is suddenly bombarded with a variety of external stimuli.The process of birth interferes with placental gas exchange, with resulting hypoxemia and hypercapnia. Also; th sensitivity of the chemoreceptors apparently increases at birth, although the mechanism is unknown. As a consequent of all these changes, the baby makes the first gasp.
459
Is the fetal lung collapsed?
No, it is inflated with liquid to about 40% of the total lung capacity. This fluid is continuously secreted by alveolar cells during fetal life and has a low pH. Some of it is squeezed out as the infant moves throughout the birth canal, but the remainder helps in the subsequent inflation of the lungs. The intrapleural pressure during the first breaths may fall -40 cm water before any air enters the lung. Expansion of the lung is very uneven at first. But pulmonary surfactant, which is formed relatively late in fetal life, is available to stabilize open alveoli, and the lung liquid is removed by the lymphatics and capillaries. Within a short time, the functional residual capacity has almost reached its normal value, and an adequate gas-exchaning surface has been established. However, it is several days before uniform ventilation is achieved.
460
How is the pulmonary vascular resistance influences after birth?
Large fall in pulmonary vascular resistance (follows the first few breaths).
461
In the fetus, the pulmonary arteries are exposed to the full systemic blood pressure via the DA, and their walls are very muscular. Result of this?
As a result, the resistance of the pulmonary circulation is exquisitely sensitive to such vasoconstrictor agents as hypoxemia, acidosis, and serotonin, and to such vasodilators as acetylcholine.
462
Several factors account for the fall in pulmonary vascular resistance at birth. Such as?
Abrupt rise in alveolar PO2, that abolishes the hypoxic vasoconstrictors and the increased volume of the lung that widens the caliber of the extra-alveoler vessels.
463
Why does the foramen ovale close?
With the resulting increase in pulmonary blood flow, left atrial pressure rises and the flap-like FO quickly closes. A rise in aortic pressure resulting from the loss of the parallel umbilical circulation also increases left atrial pressure. In addition, right atrial pressure falls as the umbilical flow ceases. The DA begins to constrict a few minutes later in response to the direct action of the increased PO2 on its smooth muscle. In
464
Why does the DA begins to constrict?
The DA begins to constrict in response to the direct action of the increased PO2 on its smooth muscle. In addition, this constriction is aided by reductions in the levels of local and circulating prostaglandins. Flow through the DA soon reverses as the resistance of the pulmonary circulation falls.
465
Exercise influence on O2 uptake and CO2 output?
Increased O2 uptake and CO2 output.
466
The environment of the fetus is very hypoxic, with the PO2 in the descending aorta being less than.....mmHg
< 25 mmHg
467
FEV
Forced expiratory volume
468
FVC
Forced vital capacity
469
In restrictive disease, inspiration is limited by the.....?
Limited by the reduced compliance of the lung or chest wall or weakness of the inspiration muscles.
470
In obstructive disease, the total lung capacity is typically abnormally.......
In obstructive disease, the total lung capacity is typically abnormally large, but expiration ends prematurely.
471
Reasons for prematurely expiration in obstructive diseases?
Early airway closure brought about by increased smooth muscle tone of the bronchi, as in asthma, or loss of radial traction from surrounding parenchyma, as in emphysema. Other causes include edema of the bronchial walls, or secretions within the airways.
472
Reasons for reduction in FEV (or FEF)
Reduced by an increase in airway resistance or a reduction in elastic recoil of the lung. It is remarkably independent of expiatory effort. The reason for this is the dynamic compression of airways. This mechanism explains why the flow rate is independent of the resistance of the airways downstream of the collapse point but is determined by the elastic recoil pressure of the lung and the resistance of the airways upstream of the collapse point. The location of the collapse point is in the large airways, at least initially.
473
Why reduction of the FEV in pulmonary emphysema?
Both due to increase in airway resistance and reduction of lung elastic recoil pressure.
474
Determination of lung volumes?
By spirometry and the measurement of functional residual capacity (FRC) by helium dilution
475
Inequality of ventilation-perfusion ratios: Why does an alveolar-arterial PO2 difference occur?
Because of regional differences of gas exchanges in the normal lung.
476
Inequality of ventilation-perfusion ratios: What does an ideal point of a O2-CO2 diagram (alveolar-arterial diagram) represent?
Hypothetical composition of alveolar gas and end-capillary blood when no ventilation-perfusion inequality is present.
477
Inequality of ventilation-perfusion ratios: What does an inequality on the O2-CO2 diagram (alveolar-arterial diagram) represents?
The arterial (a) and alveolar (A) points diverge along their respective R (respiratory exchange ratio) lines. The horizontal distance between A and a represents the (mixed) alveolar-arterial PO2 difference.
478
The (mixed) alveolar-arterial PO2 difference can in practice only be measured easily if ventilation is essentially uniform but blood flow is uneven (such as in case in pulmonary embolism), because only then can a representative sample of mixed alveolar gas be obtained. More frequently, the PO2 difference between ideal alveolar gas and arterial blood is calculated. In the case of the ideal alveoli, the .....is taken to be the same as arterial blood because the line along which point i movers is so nearly horizontal
CO2
479
Anatomic dead space
volume of the conducting airways
480
Alveolar dead space
is
481
Physiologic dead space
Includes components from the alveolar dead space and anatomic dead space
482
The PCO2 of ideal gas is very close to that of .......blood
arterial blood.
483
In normal value for physiologic dead space is about 30% of the tidal volume at rest and less on exercise, and it consists almost completely of anatomic dead space. In lung disease, it may increase to 50 % due to......
Due to the presence of ventilation-perfusion inequality
484
4 causes of low arterial PO2 or hypoxemia?
1. hypoventilation
2. diffusion impairment
3. Shunt
4. ventilation-perfusion inequality
485
Only when................does the arterial PO2 fail to rise to the expected level when 100% O2 is administered.
only when a shunt is present.
486
In diseased lungs, is the impaired diffusion always accompanied by ventilation-perfusion inequality?
Yes, in diseased lungs, impaired diffusion is always accompanied by ventilation-perfusion inequality, and, indeed, it is usually impossible to determine how much of the hypoxemia is attributable to defective diffusion.
487
There are 2 causes of an increased arterial PCO2. Which ones?
1) Hypoventilation
2) Ventiliation-perfusion inequality
(the latter does not always cause CO2 retention, because any tendency for the arterial PCO2 to rise, signals the respiratory center via the chemoreceptors to increase ventilation and thus hold the PCO2 down. However, in the absence of this increased ventilation, the PCO2 much rise.
488
Definition of compliance?
The volume change per unit pressure change across the lung.
489
How can measurement of compliance be obtained?
To obtain this, we need to know intrapleural pressure. In practice, esophageal pressure is measured by having the subject swallow a small balloon on the ned of a catheter. Esophageal pressure is not identical to intrapleural pressure but reflects its pressure changes fairly well.
(Other more simple ways also exists)
490
Definition of airway resistance?
The pressure difference between the alveoli and the mouth er unit of airflow. Can be measured during normal berthing from an intrapleural pressure record as obtained with an esophageal balloon, but also other methods.
491
How can the responsiveness of the chemoreceptors and respiratory center to CO2 be measured?
By having the subject rebreathe into a rubber bag
492
What does an affected alveolar-arterial PO2 difference reflect?
The degree of ventilation-perfusion inequality in a diseased lung
493
.......radial traction is one of the factors contributing to dynamic compression of the airways in COPD.
Loss of radial traction. Thereby reducing the FEV.
