Respiratory physiology The Essentials Flashcards
Anatomic dead space
The conducting airways contain no alveoli and therefore take no part in gas exchange
Respiratory bronchioles
The terminal bronchioles divide into respiratory bronchioles, which have occasional alveoli budding from their walls
Respiratory zone
The alveolated region of the lung where the gas exchange occurs
Acinus
the portion of lung distal to a terminal bronchiole forms an anatomical unit
conducting zone
trachea, bronchi, bronchioles, terminal bronchioles
Transitional and respiratory zones
Respiratory bronchioles, alveolar ducts, alveolar sacs
Volume of the anatomic dead region in a human?
150 ml
Volume of the alveolar region in a human
2,5-3 liters
How is the main mechanism for movement in the alveolar region
By diffusion
How big is the diameter of a capillary segment in a human?
7-10 um, just large enough for a red blood cell
Consequences of the extreme thinness of the blood-gas barrier?
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
Mean pulmonary arterial pressure required for a flow of 6 liter/min?
15 mm Hg (20 cm water)
How long time does each red blood cell spend in the capillary network?
0,75 s and during this time probably traverses 2-3 alveoli (efficient gas exchange)
Additional blood system of the lung?
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
How is the thickness of much of the capillary walls?
less than 0,3 um
How many alveoli approximately in the lungs
500 million in humans
Surface area of the lungs in humans?
50-100 square meters
Where is mucus secreted from?
By the mucus glands and also by glob let cells in the bronchial walls. The mucus i propelled by millions of tiny cilia
Cilia in the alveoli?
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.
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
Surfactant, epithelial cell, interstitial, endothelial cell, plasma, red cell membrane
How can tidal volume and vital capacity be measured
Simple spirometer
How is total ventilation calculated?
Tidal volume x respiratory frequency
What is the alveolar ventilation?
The amount of fresh gas getting to the alveoli
What is the anatomic dead space
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)
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)
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
Which volumes cannot be measured with a simple spirometer?
The goal lung capacity, the functional residual capacity, the residual volume
What is alveolar ventilation?
The volume of fresh (non-dead space) gas entering the respiratory zone per minute
How can the alveolar ventilation be determined?
Alveolar ventilation equation; CO2 output divided by the fractional concentration of CO2 in the expired gas
The concentration of …….in alveolar gas and the arterial blood is inversely related to the alveolar ventilation
CO2
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)
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
Why are the lower region of the lungs better ventilated than the upper regions?
Because of the effects of gravity on the lungs
Each acinus is supplied by……..
a terminal bronchiole
Tidal volume
Volume/amount of air entering the lung with each inspiration (500 ml ca in humans). Normal breathing
Vital capacity
The subject takes a maximal inspiration and followed this by a maximal expiration. The exhaled volume is called the vital capacity
Residual volume
The gas remained in the lung after a maximal expiration.
Functional residual capacity (FRC)
The volume of gas in the lung after a normal expiration
Which lung volumes cannot be measured with the spirometer
Total lung capacity, functional residual capacity, residual volume
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)
Alveolar ventilation
The volume of fresh gas entering the respiratory zone each minute (represents the amount of fresh inspired air available for gas exchange)
How can dead space ventilation be calculated?
Volume x Respiratory frequency.
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.
At rest, the PO2 of the blood virtually reaches that of the alveolar gas after about ………. of its time in the capillary
one-third
Blood spends only about……second in the capillary at rest
0,75 second
Blood spends about……second in the capillary on exercise
0.25 second
The diffusion process is challenged by?
exercise, alveolar hypoxia and thickening of the blood-gas barrier
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
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
How can the reaction rate of CO with Hb be altered?
By changing the alveolar PO2
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.
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.
Diffusion capacity of the lung is measured using inhaled carbon monoxide. When does the value increase markedly?
During exercise
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.
Is the carbon dioxide transfer across the blood-gas barrier diffusion limited?
Probably not
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.
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.
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
What happens with the diffusing capacity of the lung for carbon monoxide in a normal subject that exercise?
It increases
How does all gases move across the alveolar wall?
By passive diffusion
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
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.
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.
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
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.
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
What is the PO2 in a red blood cell entering the capillary normally?
40 mmHg
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
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.
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.
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.
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.
What can limit oxygen transfer into the pulmonary capillary?
Amount of blood flow available, but under som circumstances diffusion limitations also occurs.
What can limit carbon monoxide transfer?
Solely diffusion (it is therefore the gas of choice for measuring the diffusion properties of the lung)
DL: diffusion capacity of the lung equation includes the following:
area, thickness, and diffusion properties of the sheet and the gas concerned.
What can challenge the diffusion process?
Exercise, alveolar hypoxia, and thickening of the blood-gas barrier
Why is carbon monoxide often used for measurement of diffusion capacity?
Because the uptake of the carbon monoxide gas is diffusion limited.
How does exercise influence the diffusion capacity?
the diffusion capacity increases because of recruitment and distension of pulmonary capillaries
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.
How fast is the combination of O2 (or CO) with Hb in the blood after adding into the blood?
< 0.2 seconds
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
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.
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.
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).
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.
How high is the mean pressure in the main pulmonary artery?
About 15 mmHg
How high is the systolic and diastolic pressure in the main pulmonary artery?
“5 and 8 mmHg respectively
Mean pressure in the aorta?
About 100 mmHg
Pressures in the right and left atriums?
Not very dissimilar: 2 and 5 mmHg, respectively
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.
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
How is the pressure within the capillaries?
Uncertain. But the pressure within the pulmonary capillaries varies considerably throughout the lung because of hydrostatic effects.
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)
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.
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
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.
How is vascular resistance defined/calculated?
Input pressure-output pressure/blood flow
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.
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.
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.
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.
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.
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.
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
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.
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.
Example of drugs that can relax smooth muscle in the pulmonary circulation?
Acetylcholine and isoproterenol
How does high and low lung volume influence the pulmonary vascular resistance?
The pulmonary vascular resistance increases
Why does the pulmonary vascular resistance increase with alveolar hypoxia?
Because of constriction of small pulmonary arteries
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.
What can explain the uneven distribution of blood flow?
The hydrostatic pressure differences within the blood vessels.
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)
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.
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.
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.
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.
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
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)
How does NO act?
NO increases the synthesis of cyclic GMP; which leads to smooth muscle relaxation
How does inhaled NO act in scenarios of hypoxic pulmonary vasoconstriction in humans?
Reduces the hypoxic pulmonary vasoconstriction.
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)
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.
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.
How does high altitude influence pulmonary vessels/blood flow?
Generalized pulmonary vasoconstriction occurs, leading to a rise in pulmonary arterial pressure.
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.
How does a low blood pH influence the pulmonary circulation?
Causes vasoconstriction, especially when alveolar hypoxia is present.
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.
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).
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.
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)
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.
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.
What characterize the earliest form of pulmonary edema?
Engorgement of the peribronchial and perivascular spaces and is known as interstitial edema.
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
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.
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.
What happens with fluid that reaches the alveolar space?
The fluid is actively pumped out by a sodium-potassium ATPase pump in epithelial cells.
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.
Important functions of the pulmonary circulation?
4
- Move blood to and from the blood-gas barrier so that gas exchange can occur.
- 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).
- 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).
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.
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
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.
What occurs with prostaglandins E1, E2, and F2alpha in the lungs?
Become inactivated.
What occurs with norephinephrine in the lungs?
Taken up by the lung to some extent (up to 30%)
What occurs with histamine in the lungs?
Appears not to be affected by the intact lung
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).
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.
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.
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.
Does prostaglandin have vasoconstrictor of vasodilator effects?
Prostaglandins are potent vasoconstrictors OR vasodilators
Important role of prostaglandin E2 effect in the fetus?
Plays an important role in the fetus because it helps to relax the PDA.
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.
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.
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.
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.
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
Carbohydrate metabolism is also important area for the lungs. Especially the elaboration of mucopolysaccharides of…..
….of bronchial mucus.
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
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.
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.
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),
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.
Fluid movement across the capillary endothelium is governed by the …….equilibrium.
The Starling equilibrium.
The ration of total systemic vascular resistance to pulmonary circulation is about
10:1
In zone 2 of the lung; Blood flow is determined by arterial pressure minus………….pressure
minus alveolar pressure
Pulmonary vascular resistance is reduced by acutely …………. pulmonary venous pressure.
increasing
2 relatively simple causes of of impairment of gas exchange.
Hypoventilation and shunt
The PO2 of air is —–% of the total dry gas pressure (excluding water vapor)
20.93%
Barometric pressure at sea level?
760mmHg
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.
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.
4 causes of hypoxemia?
- Hypoventilation
- Diffusion limitation
- Shunt
- Ventilation-perfusion inequality.
Where does the O2 in the systemic arterial blood diffuse when reaching the tissue?
Into the mitochondria where the O2 is much lower.
How does an impaired pulmonary gas exchange influence the tissue pCO2?
Rise in PCO2
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
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)
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.
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.
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.
What is a shunt?
Blood that enters the arterial system without going through ventilated areas of the lung
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)
How is the O2 concentration of end-capillary blood usually calculated?
From the alveolar PO2 and the oxygen dissociation curve
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.
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
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.
If the shunt is caused by mixed venous blood: how can its size be calculated?
It can be calculated from the shunt equation.
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.
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.
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
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
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)
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.
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.
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.
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.
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)
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.
