Respiratory Flashcards
1
Q
What is the Po2 of air? what is the barometric pressure at sea level?
A
20.93% of the total dry gas pressure.
At sea level the barometric pressure is 760mmHg
2
Q
What is the water vapour pressure of moist inspired gas at body temperature?
A
47mmHg
3
Q
What is the Po2 of inspired air? show the calculation
A
(20.93/100) x (760-47)= 149mmHg
760 is the barometric pressure at sea level and 47 is the pressure of water vapour
4
Q
What is the PO2 in the alveoli and why ?
A
It is 100mmHg. This is because it is the balance between two processes;
1) the removal of O2 by the pulmonary capillary blood
2) continual replenishment by alveolar ventilation on the other (strictly this is not continuous but is breath by breath)
5
Q
A
5
Q
What is the fluctuation of PO2 pressure wise in the alveoli and why?
A
it is 3mmHg, because the tidal volume is small compared to the volume of gas in the lungs
6
Q
what determines alveolar PO2?
A
determined by the balance between the rate of removal of O2 by the blood (which is set by the metabolic demands) and the rate of replenishment of O2 by alveolar ventilation.
7
Q
What woul cause alveolar PO2 to drop ?
A
Increased demand that outstrips supply (e.g. fever in a brachycephalic) and decreased supply of O2 (e.g. laryngeal obstruction)
8
Q
what are causes of hypoventilation
A
Causes of hypoventilation include;
- drugs as morphine and barbiturates that depress the central drive to the respiratory muscles
- damage to the chest wall or paralysis of the respiratory muscles
- high resistance to breathing (e.g., brachycephalic)
- Some diseases, such as morbid obesity may cause hypoventilation by affecting both central respiratory drive and respiratory mechanics.
9
Q
What physiological change does hypoventilation always cause
A
an increased alveolar, and therefore arterial Pco2
10
Q
what is the alveolar ventilation equation?
A
Pco2= (Vco2/Va)xK
Vco2 = patient CO2 production
Va= alveolar ventilation
K= constant
11
Q
Define and what is the alveolar gas equation ?
A
The relationship between the fall in PO2 and the rise in Pco2 that occurs with hypoventilation
PA02 = PIo2 - (PAco2/R) +F
F= small correction factor (usually 2mmHg for air breathing) which is often ignored.
12
Q
What happens to alveolar and arterial O2 in hypoventilation
A
It is ALWAYS reduced EXCEPT when the individual breaths an O2 enriched mixture. In this case the amount of O2 per breath makes up for the reduced flow of inspired gas
13
Q
If a patient was hypoventilating, and then suddenly starts hyperventilation, why does it take several minuted for the alveolar PO2 and PCO2 to assume their new steady-state values?
A
Because there are significant higher stores of CO2 in the body in the form of bicarbonate and interstitial fluid.
14
Q
Is the PO2 of arterial blood the same as alveolar gas?
A
At the level of the alveolus it should be, however, the arterial blood never quite reaches it.
This is due to;
- incomplete diffusion through the blood gas barrier ( not usually a problem at sea level even when lung disease is present as the RBC spends enough time in the pulmonary capillary to become saturated)
- Shunts;
1) Blood that enters the arterial system without going through ventilated areas of the lung. In the normal lung, some of the bronchial artery blood is collected by the pulmonary veins after it has perfused the bronchi and its O2 has been partly depleted.
2) small amount of coronary venous blood that drains directly into the cavity of the left ventricle through the Thebesian veins.
3) other congenital abnormalities (Pulonary arteriovenous malformation)
The effect of the addition of this poorly oxygenated blood is to depress the arterial PO2.
15
Q
Draw a schematic of O2 transger from air to tissues showing the changes in arterial PO2 on the Y axis
A
16
Q
What is the alveolar shunt
A
Blood that enters the arterial system without going through ventilated areas of the lung. In the normal lung, some of the 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.
17
Q
What cardiac pathologies can result in a lower PO2 even when alveolar ventilation is normal ?
A
Any right to left shunt
18
Q
How do you calculate shunt flow ?
A
Qs/Qt = (Cc’o2 -Cao2) / Cc’o2 -CvO2)
Qt= total amount of O2 leaving the system
CaO2= O2 concentration of the arterial blood.
19
Q
How do you abolish hypoxemia in a shunt?
A
You cannot. Even giving 100% O2 will not result in this as CO2 is generated by the metabolism and it will shunt this into the arterial system
20
Q
Is it pointless to give shunt patients 100% O2
A
No, even though the shunt is still reducing PO2, giving 100% O2 will help relieve some symptoms as the patient will have increased dissolved O2 concentrations (ie non haemoglobin bound)
21
Q
why can you diagnose a shunt by giving 100% O2
A
When100%O2 is inspired, the arterial PO2 does not rise to the expected level—a useful diagnostic test.
Giving the subject 100% O2 to breathe is a very sensitive measurement of shunt because when the PO2 is high, a small depres- sion 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
22
Q
A shunt usually does not result in a raised PCO2 in arterial blood, even though the shunted blood is rich in CO2. Why?
A
The reason is that the chemoreceptors sense any elevation of arterial PCO2 and they respond by increasing the ventilation. This reduces the PCO2 of the un-shunted blood until the arterial PCO2 is normal. Indeed, in some patients with a shunt, the arterial PCO2 is low because the hypoxemia increases respiratory drive
23
Q
What are the 4 causes of hypoxemia;
A
1) hypoventilation
2) diffusion
3) shunt
4) ventilation/perfusion missmatch
24
What is ventilation- perfusion missmatch
This is when the ventilation and blood flow are missmatched in various regions of the lung resulting in impairment of bth O2 and Co2 to transfer
25
what determines the ratio f gas in any particular lung unit at any point in time ?
In exactly the same way, the concentration of O2 (or, better, PO2) in any lung unit is determined by the ratio of ventilation to blood flow. This is true not only for O2 but CO2, N2, and any other gas that is present under steady- state conditions.
26
what happens when you reduce ventilation-perfusion ratio - e.g. by a gradual obstruction to ventilation (blood flow unchanged)?
The O2 in the unit will fall, and the CO2 will rise
27
In V/Q missmatch, what happens if you gradually obstruct blood flow ?
The O2 rises, and the CO2 falls enventually reaching the composition of the inspired air
28
What is the ventilation-perfusion ratio equation
29
Depict the O2-Co2 diagram showing ventilation-perfusion ratio
30
where is the ventilation-perfusion difference greatest in the lung and why?
At the top of the lung, as the ventilation slowly increaes from top to bottom of the lung and blood flow increases more rapidly. It is clear that the PO2 of the alveoli (horizon- tal axis) decreases markedly down the lung, whereas the PCO2 (vertical axis) increases much less. Ventilation is less at the top than the bottom, but the differences in blood flow are more marked.
31
Depict the V/Q based on location within the lung
It is clear that the PO2 of the alveoli (horizon- tal axis) decreases markedly down the lung, whereas the PCO2 (vertical axis) increases much less. Ventilation is less at the top than the bottom, but the differences in blood flow are more marked.
32
How does pH vary in the lung ?
It is lower at the apex as PCO2 there is higher, while it increases more towards the base. This reflects the PCO2 variation
33
How does exercise change the distribution of blood flow throughout the lungs?
It becomes more uniform, and the apex assumes a larger share of the O2 uptake
34
Chart the changes in Po2 when there is no shunt and a shunt
`
35
What are the 4 causes that cause the O2 disassociation curve to shift to the left and right?
Higher CO2: Increased CO2 levels lead to a decrease in pH (acidosis), shifting the curve to the right, promoting oxygen unloading in tissues.
Lower pH: A more acidic environment (lower pH) decreases oxygen affinity, causing a right shift.
Higher Temperature: Increased body temperature increases the need for oxygen, shifting the curve to the right, facilitating oxygen delivery to tissues.
Increased 2,3-DPG: Elevated levels of
2,3-DPG decrease oxygen affinity, leading to a right shift.
36
Which type of pneumocytes synthesize pulmonary surfactant?
Type II
37
Why do the alveoli contain phagocytic cells (alveolar macrophages)?
To keep the alveoli free of dust and debris because the alveoli have no cilia to perform this function
38
The walls of the conducting airways contain what type of muscle, and what type of innervations does that muscle have?
Smooth muscle; both sympathetic and parasympathetic innervations
39
What is functional residual capacity (FRC?)
The volume remaining in the lungs after a normal tidal volume is expired
40
What is Boyle's law?
- A gas law that states that the pressure exerted by a gas is inversely proportional to the volume occupied by it
- The pressure and volume of a gas are inversely proportional to each other as long as the temperature is kept constant
41
Explain the difference between anatomical and physiological dead space
Anatomic dead space is the volume of gas in the conducting airways whereas physiologic dead space is the total volume of the lungs that does not participate in gas exchange --> physiological DS includes anatomic DS plus a functional dead space in the alveoli
42
What is functional dead space?
Ventilated alveoli that do not participate in gas exchange
43
What is the most important reason that alveoli do not participate in gas exchange?
V/Q mismatch
44
Why can we assume that PCO2 of arterial blood is equal to the PCO2 of alveolar air since alveolar air cannot be measured?
Because alveolar air is normally equilibrated with pulmonary capillary blood, which becomes systemic arterial blood
45
What is the equation to calculate minute ventilation?
TV x BPM
46
What is alveolar ventilation?
Minute ventilation corrected for physiologic dead space
47
What is the equation to calculate alveolar ventilation?
Va = (Vt - Vd) x BPM
Va = alveolar ventilation
Vt = tidal volume
Vd = physiologic dead space
48
Is the relationship between alveolar ventilation and alveolar PCO2 linear or inverse?
Inverse
49
What is the respiratory quotient for veterinary patients?
0.8
50
'Lung compliance' describes what?
The change in lung volume for a given change in pressure
51
Is the compliance of the lungs and chest wall linear or inverse?
Inverse
52
Surfactant, a phospholipid, is produced by what type of cells?
Type II alveolar cells
53
What is hysteresis?
The two different slopes of the expiration and inspiration loop of the lung compliance curve (ch 5, page 205)
54
Why are the inspiration and expiration limbs of the lung compliance curve (ch 5, pg 205) different (hysteresis)?
The difference in surface tension at the liquid-air interface of the air-filled lung --> the intermolecular attractive forces between liquid molecules lining the lungs are much stronger than the forces between liquid and air molecules
55
How do small alveoli remain open under high collapsing pressures?
Surfactant reduces surface tension, which then reduces the collapsing pressure for a given radius
56
What is the most important constituent of the composition of surfactant?
DPPC = dipalmitoyl phosphatidylcholine
57
What is the law of Laplace?
It states that the pressure tending to collapse an alveolus is directly proportional to the surface tension generated by the molecules of liquid lining the alveolus and inversely proportional to alveolar radius
58
Based on the law of Laplace, would a large alveolus (aka one with a large radius) have a high or low collapsing pressure?
Low due to the inverse relationship and will require less pressure to keep it open
59
Based on the law of Laplace, would a small alveolus (aka one with a small radius) have a high or low collapsing pressure?
High due to the inverse relationship and will require more pressure to keep it open
60
What is the mechanism by which DPCC reduces surface tension?
Due to the amphipathic nature of the phospholipid molecules (hydrophobic on one end and hydrophilic on the other)
61
What are 3 advantages of surfactant?
1. Surface tension and collapsing pressure are reduced and small alveoli are kept open
2. Increases lung compliance
3. Keeps alveolar size relatively uniform
62
Why is it beneficial for alveoli size to be relatively uniform?
During inspiration, some alveoli inflate more quickly than others. Such unevenness of ventilation would impair gas exchange
63
____ difference is the driving force of air flow being able to occur
Pressure
64
Airway resistance is determined by which law?
Poiseuille's
65
What is the principle of interdependence of alveoli?
Alveoli tend to hold their neighbors open by radial traction or mechanical tethering. When they are more inflated, they pull on both adjacent alveoli and nearby bronchioles, pulling the bronchioles open and decreasing their resistance
66
What is Dalton's law?
It states that the total pressure of a mixture of gases is equal to the sum of the partial pressures of individual gases
67
What is Henry's law?
The amount of dissolved gas in a liquid (blood) is directly proportional to the partial pressure of that gas above the liquid when the temperature is kept constant
68
What is Fick's law?
Diffusion - that particles will move from higher concentration to lower concentration
69
What is the driving force for diffusion of a gas?
The partial pressure difference of the gas (NOT the concentration difference)
70
Do bound gas and chemically modified gas contribute to partial pressure?
No, only dissolved gas molecules contribute to partial pressure
71
Of the gases found in inspired air, which is the only one that is carried ONLY in dissolved form and is never bound or chemically modified?
Nitrogen - this is why it is sometimes used for certain measurements in respiratory physiology
72
What is the pressure of water vapor?
47 mmHg
73
Dissolved oxygen, on its own, is (sufficient/insufficient) to meet the metabolic demands of the tissues
Insufficient
74
How many subunits does hemoglobin have?
4
75
For the hemoglobin subunits to bind oxygen, iron in the heme moieties must be in the (ferrous [Fe2+] OR the ferric [Fe3+]) state?
Ferrous state [Fe2+]
76
If the iron component of the heme moieties is in the ferric (Fe3+) state, it is called____?
Methemoglobin
77
what does ficks law of diffusion state?
The amount of gas that crosses sheet of tissue, is proportional to the area of the sheet, but inversely proportional to the thickness.
Hence the lungs have a massive surface area and the alveolar endothelium is very thin.
78
How do O2 and CO2 cross into the blood?
Define partial pressure?
By simple diffusion. AKA from high partial pressure to low partial pressure.
Partial pressure of a gas is found by multiplying its concentration by the total pressure.
E.g. Dry air is 20.93% O2, and its partial pressure at sea level is 760mmHg; so, (20.93/100) x760 =159
-Divide by 100 as the concentration is a percentage
79
How does air move down the main airways and then the terminal bronchioles and alveoli?
The main airways (conduction zone)flow goes down a pressure gradient by bulk flow. However, once you reach the terminal bronchioles, due to all of the divisions in parallel, the total cross sectional area of the airways is enormous and bulk flow stops. At this stage, ventilation is due to the diffusion of O2 into the blood which takes over as the main mechanisms of ventilation.
80
How is capillary vessel layout optimised for gas exchange?
Each capillary is only7-10um in diameter, enough for a red blood cell, however, the capillarie segments are very short and continuosy branching. This forms such a dense network of blood vessles that it forms nearly. a continous sheet of red blood cells.
81
What is a defect of having dense network of blood vessels with extremely thin walls around the alveoli?
That large increases in capillary pressure can damage the barrier and cause leaking into the alveoli
82
what is the bronchial circulation, and how important is this?
this is systemic circulation that carries blood down to the terminal bronchials and no further. This blood then mostly drains into the venous system, with a small amount going into the arterial (physiological shunt). This helps O2 delivery to poorly ventrilated tissues ( thicker tissues) but, flow through this is a mere fraction of the pulmonary circulation and the lungs can work without it (transplantation)
83
How are debries removed by the lungs?
in the bronchioles, goblet cells secrete mucous which traps debris. The mucous is then transported up the airway via cillia and coughed out. The alveoli do not have cillia though, so they use macrophages which engolf material and are then transported out of the alveolus by the lymphatics. Leukocytes can also participate in host defences
84
What is tidal volume?
Dead space?
Vital capacity ?
Functional residual capacity?
Minute ventilation?
Alveolar ventilation ?
- amount of air entering the lung with each respiration
- Airways not involved in gas exchange (conduits)
- Air expelled after a maximal inspiration followed y maximal expiration
- Functional residual capacity is the amount of air left in the lung after each normal breath
- the amount of total volume entering/leaving the lungs per minute.
- The total volume reaching the alveoli per minute (tidal volume - dead space x breath per min)
85
If the alveolar ventilation is calculated by subtracitng dead space from the tidal volume, why does the alveolus expand to account for the total inspired air (inc dead space) ?
Because when new fresh gas reaches the alveolus it pushes the dead space air from the previous breath into the alveolus ?
86
What does dead space volume depend on in a healthy patient?
Posture and size of the patient and the depth of the breath. The large the breath, the more traction the lung parenchyma places on the airways enlargening them.
87
which gas diffuses better from the alveolus into the blood and by how much?
CO2 is more solluble and diffuses 20x better than O2
88
what is the difference between perfusion and diffusion limted transfer of gas. Give examples of extremes and for O2
Carbon monoxide (CO) moves accross the capillary membrane rapidly, and therefore, the content of CO in the RBC raises rapidly. However, because CO has a very strong affinity for the haemoglobin the CO partial pressure in the blood hardly changes. As a result, the amount of carbon dioxide that gets into the blood is limited by the diffusion properties of the blood-gas barrier - > diffusion limited .
Nitrous oxide, when this moves into the blood, there is no combination with haemoglobin. As a result, the partial pressure of this rises rapidly as it is all left in blood. Thus the amount taken up is entirely dependent on the amount of blood flow -> perfusion limited
O2; between CO and N2O as it combines with haemoglobin, but not with the avidity of CO. Additionally, as capillary blood is mixed venous, the PO2 of the RBC is is already 4/10 of the alveolar value, and the RBC reaches the alveolar value by the time its 1/3rd of the way through the capillary.
89
If there is thickening of the blood-gas barrier, what changes may we see in PO2?
The partial pressure will take longer to rise. Normally the haemoglobin is saturated by the time the RBC is 1/3rd of the way though the capillary, however, with thickening it may take until the end of the capillary, or it may not completely saturate
90
When does haemoglobin become fully satturated with O2 in a normal patient?
Once the partial pressure of O2 in the alveolus is the same as the RBC. The RBC entering the capillary has a PO2 of ~40mmHg, while the alveolus PO2 is 100mmHg. Usually the RBC will reach a PO2 of 100mmHg by the time it is 1/3 of the way through the capillary.
91
How does Oxygen uptake vary with intense exercise in a normal individual and why?
What changes in PO2 do we see?
It does not.
With increased Cardiac output from exercise, flow in the capillaries increases. The amount of time a RBC will spend in the capillary will drop and can reach as little as 1/3rd of the normal time (0.75s). However, in normal non exercising individuals, the RBC PO2 will match the alveolar PO2 by the time the RBC is 1/3rd of the way through the capillary. Thus, there is no difference in PO2 because it occurs within the same interval of time.
92
How does Oxygen uptake vary with thickening of the blood gas barrier and why?
What changes in PO2 do we see?
Thickiening of the barrier (based on Ficks law) will increase the amount of time it takes the O2 to diffuse into the blood and therefore RBC. This, if bad enough, may not allow the RBC PO2 to reach that of the alveolus within the 0.75s it takes for the red blood cell to cross the alveolus and we may see a drop in PO2.
93
What normal environmental conditions would cause alveolar PO2 to drop?
How would this affect RBC PO2 and give an axample that is compared to normal?
being in an oxygen poor environment (high altitude).
Normal, the Alveolar PO2 is 100mmHg, the RBC entering the capillary is ~40mmHg, giving a pressure difference (ie driving force) of 60mmHg from the alveolus into the RBC.
If you are in an environement where your alveolar PO2 is only 50mmHg, the RBC PO2 will be about 20mmHg (the previos breath did not allow for enough O2 to enter the blood, hence, the drop from 40mmHg [Alveolar PO2 is half, therefore, RBC PO2 is half), which gives a pressure difference of 30mmHg. Because of the smaller pressure difference there is now less driving force pushing O2 into the blood and RBC, so O2 moves accross more slowly. As a result, and because of the steep slope of the oxygen association curve (where it binds more quickly initially) there is a possibility that the PO2 between the alveolus and the RBC will not equilibrate.
94
what gas is used when measuring the perfusion properties of the lung in vivo?
Carbon monoxide as this is limited SOLELY by diffusion.
95
What are the two stages of O2 uptake
1) diffusion of O2 through the blood gas barrier (including plasma and RBC interior)
2) reaction of O2 with haemoglobin
DL = Vgas/(P1-P2)
I.e flow of gas divided by a pressure difference
96
What is meant by transfer factor ?
How much O2 is transfered onto the haemoglobin. this takes into account not only diffusion through the blood gas membrane but also perfusion to the lung, as you can have
- Normal perfusion, decreased diffusion
- Decreased perfusion, normal diffusion
- Decreased perfusion and diffusion
97
How does CO2 diffusion differ from O2
it is 20x faster
98
what is the pulmonary artery pressure?
What is the pressure in the aorta?
What is the difference in left and right atrial pressure and how does this change pressure difference at the outlet of each major vessel.
25/8 (15)
100-120/90-80
La 5, RA 2
Thus, the difference in pressure between the Ao and RA is 98mmHg, while between the PA and LA it is 10mmHg (15mmHg-5mmHg)
99
when measuring pulmonary artery pressures we use mean, while for systemic we use systolic. Why ?
Aortic pressure waveform is high-pressure and pulsatile, with significant difference between systolic and diastolic values.
- Systolic Aortic Pressure (SAP) reflects peak left ventricular ejection pressure, which is clinically relevant as we are looking at determining left ventricular fucntion, coronary perfusion etc.
- also this is measured peripherically where systloic readings are more accurate
Pulmonary artery pressure (PAP) is lower-pressure and the waveform is dampened, with smaller systolic-diastolic difference.
- Mean PAP better reflects overall pulmonary vascular load and is more useful clinically and hemodynamically for determining whethere there are perfusion issues, pulmonary hypertension etc. Additionally, this is only measured invasively so mean accuracy is not lost.
100
why is the systemic blood high pressure and pulmonary low pressure
The systemic has to pump blood to all regions of the body, some of which are significantly higher than the heart its self. Additionally, there is often local changes with individual organs which affect blood flow, or where aditional pressure maybe required.
The pulmonary system, lies for the most part in parallel with the hear (esp quadipreds, less so in bipedal mammals). Also, the pulmonary system diverts all of the CO to one organ, where there are less perfusion changes over time, thus it does not need to generate much pressure to allow perfusion (enough to allow it to push past the pressure in the RA). Finally, the capillaries have very little force generated around them ad mostly surrounded by air in the alveolu (there is a membrane, but it is so thin it provides nearly no support), thus they are very prone to collapse if pressure around them increases, while if pressure indide the vessel increases, due to the fenestration, you get oedema.
This allows the right heart to minimise force generation and energy utilisation
101
what is transmurral pressure?
What is it for the pulmonary capillaries
the pressure diffence between the inside and outside of the capillaries. Transmural pressure in healthy lung capillaries is negligeable.
102
What is the transmural pressure for the main pulmonary artery and vein
The pressure around the major vessels can be considerably less than alveolar because of the negative pressure creates in the chest with respiration. As the lung expands, these larger vessels are pulled open by the radial traction of the eleastic lung parenchyma that surrounds them. Consequently, the effective pressure around them is low (there is evidence suggesting that this pulling reduces the pressure to bellow that of the pressure around the lungs as a whole [intrapleural pressure]). As the lung expands, the radius of the vessel dilates, the resistance in the vessel goes down (pouisille) and the blood pressure in the vessel goes down)
103
what are alveolar vessels and extra-alveolar vessels?
terms used for capillaries and pulmonary arteries and veins respectivelly. Termed this way as the change in pressure within the vessels so very different with respiration
pulmonary - no signficant change as capillary pressure is similar to alveola
Extrapulonary - as lung expands pressure drops as the walls of the vessels are pulled wider.
104
how do you calculate vascular resistance simplistically ?
Vascular resistance = (Input pressure-output pressure)/blood flow
105
Pulmonary vascular resistance is 1/10th of systemic. How do we know this to be true?
The pressure drop from PA->LA is 10mmHg, while from AO->RA it is nearly 100mmHg. Becuase the blood flow through the two circulations is virtually identical, we can determine that the SVR in the pulmonary system is 1/10th of the systemic
106
why is the systemic resistance higher than the pulmonary?
mainly due to the very muscular vessles of the systemic circulation and due to receiving organ changes in blood flow
107
How is it that pulmonary SVR reduces with increased pulmonary vessel blood pressure?
1) some capillaries are closed in normal conditions which may open with increased BP leading to reduced overall resistance -> recruitment
2) widening of individual capillary segments can occur at higher pressures.
3) increase in perfusable tissue which would not otherwise be collapsed around the vessles increasing radial force and therefore SVR ->critical operating pressure
108
what is critical operating pressure?
When can example of this be seen?
this is the pressure needed to reperfuse segments of lung that would otherwise be physiologically collapsed (ie physiological dead space)
-> when a normal idividual takes a deep breath you will see a drop in the pulmonary blood pressure.
i.e. a collapsed piece of tisse crimples the blood vessels reducing their diameter.
109
How can you calculate the volume of blood passing through the lung each minute?
Fick principle;
O2 consumption per minute (VO2) measured at the mouth, is equal to the amount of O2 taken up by the blood in the lungs per minute. VO2 is measured by collecting expired gas in a large spirometer and measuring its O2 concentration.
110
why is the a difference in perfusion between more dorsal and more ventral lobes?
More ventral tend to have more perfusion due to the hydrostatic pressure differences within the blood vessels (pressure drops pumping up hill)
111
How does the difference in regional perfusion change with anaesthesia and exercise
All regions receive perfusion in the normal lung as capillary hydrostatic pressure is enough to prevent vessel collapse. With exercise, the presseure, and therefore perfusion, changes between the regions get narrower. with anaethesia, a dependent region may collapse, as the drugs lower the hydrostatic pressure in the capillaries, and the dependent ones maybe flattened under the weight of the body ontop (actelectasis)
112
what is hypoxic pulmonary vasocostriction ?
Exact mechanism is not known. This is when there is vasocostricting in response to hypoxia, and it occurs chiefly when he PO2 of the alveolar gas is low, rather than the blood its self. This does not depend on the nervous system as it occurs in excised lungs.
At 100mmHg of alveolar Po2 there is no vasocostriction. With 70mmHg there is severe vasocostriction, lower still blood flow maybe inhibited completely
113
what happens with disruption of eNOS gene in small animal model?
Why?
Severe pulmonary hypertension
eNOS (endothelial nitric oxide synthase) catalyses L-arginine to Nitric Oxide (NO). Nitric oxide, released by the endothelium, binds NOr receptor and increases the activity of Guanosine-3,5-monophophate which produces cyclic GMP. cGMP subsequently inhibits Ca channels, preventing a rise interacellular Ca which causes vasodilation. This lack of cGMP production due lack of eNOS causes pulmonary hypertension
114
what are potent capillary endothelial vasocostrictors?
How do they work?
Endothelin-1 (ET-1) and Thromboxan A2 (TXA2).
ET-1 released by endothelium -> ET-1 binds ETA on vasular smooth muscle -> PLC -> PIP2 and DAG -> DAG increases Ca channel opening -> vasocostriction
Membrane phospolipids -> synthesise arachydonic acid -> COX1 and COX2 synthesisse prostaglanding E2- > synthesises thromboxane A2 -> vasocosntrics, increases platelet aggregation and bronchioconstrict
115
what is the benefit of hypoxic vasocostriction ?
it diverts blood away from the lung regions where there is hypoxia minimising deleterious effects
116
in what circumstances may you see hypoxic vasocostriction in healthy individuals ?
High altitude - there is decreased PO2 to all regions of the lung which results in generalised pulmonary vasocostriction leading to a rise in pulmonary arterial pressure.
Faetal life; there is no O2 being delivered to the lungs and therefore there is alveolar hypoxia. This marked vasocostriction with only 15% of CO going to the lungs . when the first breath reaches the alveoli, the alveolar hypoxia is obliterated which downregulaes TXA2 and ET1. Also, prostaglandin drops drammatically which is the precursor for TXA2 production
117
What law do the alveoli follow to keep water out and in the blood vessels?
Explain;
Starlings law; the force tending to push fluid out of the capillary is the capillary hydrostatic pressure - the hydrostatic pressure of the interstitial fluid (Pc-Pi). The force tending to pull fluid is the colloid osmotic pressure of the proteins in the blood - that of the proteins in the intestitial fluid (πc-πi). This force depends on the reflection coeficient σ, which is a measure of the effectiveness of the capillary wall in preventing the passage of proteins accross it;
Net fluid out = K[Pc-Pi]-σ[πc-πi]
K is filtration coeficient = 1.00 × 10−3 cm3 sec−1 cm H2O−1
σ= 0.35
118
where do small volumes of fluid go when they leaks out of the capillaries?
if small enough in volume the lymphatics will absorb it (large network), othewise it can cause oedeama.
119
what is the first non clinical sign of oedema histiologically ?
there is engorgement of peribronchial and preivascular spaces with local lymphatic dilation - > interstitial oedema
This is why cats can get chylothorax with failiure, as the lymphatics become engorged (in addtion to the thoracic duct draining into the cranial vena cava [or sometimes subclavian and brachycephalic vein])
120
why do cats get chylous effusion with heart failiure?
Fluid leaving out of the capillaries fills the interstitium increasing the hydrostatic pressure of this. The excess fluid is partially absorbed by a large network of lymphatics at the gas-blood interface which becomes congested.
In addtion to the thoracic duct draining into the cranial vena cava [or sometimes subclavian and brachycephalic vein].
121
How does the alveoulous attempt to clear pulmonary oedema?
It is actively pumped out by Na:KATPase in the epithelial cells
122
Other than gas exchange, what are the roles of the lungs?
Blood resevoire
Blood filter - some drugs are pulmonary excreted (e.g. iso, alcohol, serotonin)) - includes filter for small thrombi
White blood cell resevour
Hormonal - eg ACE production and conversion of AngI->AngII, Bradykinin inactivation (80%), phospholipids (via phopholipase A2) produce arachydonic acid (for leukotrense, prostaglanding, thromboxane A2 etc)
Clotting; large mast cell population which contains heparin in the interstitium
123
IF you inspire O2 at a PO2 of 150mmHg, it will have fallen to 100mmHg in the alveoli. Why?
The Po2 of alveolar gas is determined by two processes;
1) the removal of O2 by pulmonary capillary blood
2) continous replenishment of alveolar O2
124
what are the 4 causes for hypoxemia;
1) hypoventilation
2) diffusion limitation
3) shunt
4) ventilation-perfusion inequality
125
what is PO2 at the level of the albeolous dependent on?
1) the rate of CO2 removal ([CO2] dependent based on metabolic need)
2) rate of O2 refreshment at the alveoli
126
Define hypoventilation?
The PO2 at the alveoulus is determined by;
1) the rate of CO2 removal ([CO2] dependent based on metabolic need)
2) rate of O2 refreshment at the alveoli
Thus if alveolar ventilation is abnormallylow, the alveolar PO2 falls, and for similar reason PCO2 rises -> hypoventilation
PCo2 = (Vco2/Va)xK
Vco2 - production of Co2
Va= alveolar ventilation
K= diffusion constant
The relationship between alveolar ventilation and PCO2 means that with halving of ventilation, we double the CO2
127
What change would you see on blood work with hypoventilation ?
As the CO2 accumulates in the alveolus, we see a rise in arterial PCO2.
128
If you have a patient which has been hypoventilating for some time and is hypoxic. by inducing normal or hyperventilation, how long do you expect it to take to normalise the PO2
Several minutes because there are significantly higher stores of CO2 than O2 in the body. This is because CO2 is stored in the form of bicarbonate in the blood and the interstitial fluid.
the oposite occurs with the onset of hypoventilation
129
when do diffusion limitation cause hypoxia and why ?
Rarerly at sea level.
Technically the capillary PCo2 never actually reaches that of the alveolus, but the difference is immeasurably small. However, the gap will get larger with exercise, although this will not cause hypoxia at sea level in a normal person. Barely ever in lung disease ether.
You need severe thickening of the endothelium of the blood vessel, increased interstitium, or poor O2 mixture is breathed in
130
what is a shunt?
venous blood that enters the arterial system without going through the ventilated parts of the lung (e.g. cardiac shunts, pulmonary arteriovenous malformations etc). p
Adding this deoxygenated blood lowers capillary CO2.
131
what is a normal physiological shunt?
small amount of venous blood that enters the left ventricle through the thesbian veins that drain blood from the coronary arteries
132
what is the most likely diagnosis, if you give a patient O2 and there is no change in SPO2?
IT is likely a shunt as these supplemental oxygen is not able to undo the CO2 pumped by the shunt. You will see a mild increase in O2 as this disolves into the blood. However, you cannot correct the hypoxia
133
why would a shunt not cause a raise in arterial PCO2?
The chemoreceptors sense any elevation in arterial PCo2 and hey respond by increasing ventilation removing the CO2. This can happen to such a degree that the PCO2 will actually be low.
134
what is ventilation/perfusion missmatch?
V/Q mismatch in the lungs occurs when there's an imbalance between the amount of air reaching the alveoli (ventilation) and the amount of blood flowing through the capillaries around those alveoli (perfusion). Essentially, it means some parts of the lungs are well-ventilated but under-perfused, or vice versa, leading to inefficient gas exchange
135
For the following, state the A-a difference and the response to O2;
1) hypoventialtion
2) Diffusion limitation
3) Shunt
4) Va/Q inequality
1) A-a NONE; O2 response, GOOD
2) A-a INCREASED; GOOD
3) A-a INCREASED; SMALL
4) A-a INCREASED; GOOD
136
what is the main difference between a fully areated lung and one with ventilation perfusion missmatch when looking at PO2 and PCO2
A V/Q missmatched lung cannot mantain as high an alveolar PO2 or as low a PCO2 as one that is fully areated
137
what is the A-a difference?
this is the difference in arterial O2 (A) and alveolar O2 (a). This is the normal upright patient is minimal. However, with diffusion limitations (there is more CO2 in A), shunt (more CO2 in A) and V/Q missmatch ( ether A or a can have more CO2 depending on which is affected) we see a increase in the difference. Hypoventilation does not affect A-a because less air is being delivered to the lung (thus less A) but, less Co2 is being breathed off ( more CO2 in a)
138
what is Henry's law?
How does this apply to the normal individual?
the amount of disolved O2 is proportional to the partial pressure of O2.
For each mmHg there is 0.003ml 02 per 100ml of blood. Thus normal arterial PO2 of 100mmHg contains 0.3ml O2 in 100ml
139
Why is disolved O2 not sufficient to meet metabolic demands?
Henry's law states that the average person will have a disolved O2 deliver of ~90ml/min to the tissues. However, the normal person may have a metabolic demans as high as 3000ml/min
140
Describe the structure of haemoglobin?
Iorn porpyrin compound joined to four polypeptide chains that together form a globulin protein. There are two chain types, Alpha and Beta and the difference in their ammino acid sequence is what gives rise to the various types of haemoglobin.
141
What are the various types of Haemoglobin;
Haemoglobin A = adult
Haemoglobin F= foetal (high O2 affinity due to the highly hypoxic environement)
Disease forms ;
Haemoglobin S= sickle - has valine insead fo glutamic acid in their ß chain reducing O2 affinity.
There are other physiological types that are not involved in O2 and Co2 transport such as carboxyhaemoglobin, haem-haemoglobin
142
how is methemoglobin formed ?
Why does this matter>
This is haemoglobin A which has reacted to various drugs (nitrited, sulfonamides, acetanilide etc) which converts ferrous haemoglobin to ferric.
The ferric form does not dissassociate from O2 very well, which makes it challenging for O2 transfer from the blood to the tissue.
143
Explain what is meant by the oxygen association with heamoglobin is not linear
Up to a PO2 50mmHg, the oxygen association with haemoglobin is approximately linear. Above that range, the curve starts to flatten out. The O2 capacity, ie the maximum O2 that can bind to haemoglobin, is the maximum O2 that can bind, ie when all the oxygen carrying sites are occupied. This is, in blood with a PO2 of 100mmHg is about 97.5%, whereas in mixed venous blood with a Po2 of 40mmHg it is 75%.
The reason the curve starts to flatten is because the haemoglobin has such high affinity that a lot of the binding sites are already occupied by dissoved O2 by the time the RBC reaches the oxygen rich lung. Thus, despite this marked increase in O2 availability, there is not much carrying capacity left on the haemoglobin. This is a buffering system to make sure that the RBC is able to maximally load its self with oxygen even with drops in PaO2.
The linear initial association is also due to haemoglobin conformational change. As O2 binds, there is a change from the T form (Tense) to the R form (relaxed). As the shape changes, O2 affinity increases thus, the linear growth, until nearly all the association sites are taken where the plateau starts to kick in.
144
What is T->R conformational change in haemoglobin?
Hemoglobin changes shape when binding to oxygen due to allosteric interactions between its subunits, a process called cooperativity. When one oxygen molecule binds, it triggers a conformational change that makes it easier for subsequent oxygen molecules to bind. This change in shape leads to a sigmoidal (S-shaped) oxygen-hemoglobin dissociation curve, indicating that hemoglobin's affinity for oxygen increases as more oxygen molecules bind
145
what happens to O2 and CO2 affinity to haemoglobin as CO2 builds up in the blood stream during exercise ?
What is this effect called?
In the presence of CO2, the pH of the blood decreases, causing hemoglobin to change shape, reducing its affinity for oxygen, and promoting oxygen release into tissues, and increasing its affinity for CO2 where it can take it back to the lungs for release.
i.e. simultaneously destabilizing the high-affinity R state and stabilizing the low-affinity T state
IT is called the Bohr effect
146
how do you calculate O2 saturation of Hb?what is this?
O2 saturation of Hb is the percentage of the available bindinf sites that have O2 attached and is given by;
(O2 combined with Hb/O2 capacity) x100
147
what are the physiological advantages of the curved shape of the Hb dissassociation curve?
1) O2 saturates Hb even when alveolar gas drops somewhat (the steep flat part)
2)As RBC uptake O2 along the capillary, a large partial pressure difference between alveolr gas and blood developes hastening diffusion
3) The steep lower part of the curve means that peripheral tissues can withdraw a large amount of O2 for a small drop in PaO2
148
What does shifting of the heaemoglobin dissasociation curve to the right mean, and when does this happen?
Why does it happen?
It means higher PaO2 concentration is needed for the haemoglobin to start saturating with O2 (Ie oxygen affinity of Hb is lower) . This occurs in acidosis (H+), PCO2 (ie more acid), temperature and concentration of 2,3-diphosphoglycerate (DPG) in the red cells.
It happens due to changes in the haemoglobin conformation which make it less affine to O2.
149
what is the Bohr effect?
increase in PCO2 increases H+ causing conformational changes in haemoglobin decreasing its affinity to O2. The benefit of this is that it releases more O2 into the blood too which increases O2 availability
i.e it simultaneously destabilizing the high-affinity R state and stabilizing the low-affinity T state,
150
what is 2,3 diphosphoglycerate and how does it affect oxygen binding to haemoglobin?
What causes 2,3-DAG to increase in concentration ?
2,3-DPG is an end product of RBC metabolism. This shifts the O2 disassociation curve to the right reducing the haemoglobin affinity for O2
Increased concentrations of 2,3-DAG are seen in chronic hypoxia, increased altitude and the presence of chronic lung disease
151
What is P50?
P50 is the PO2 for 50% saturation (ie when the haemoglobin dissassociation curve starts to flatten)
152
what are the 3 forms of CO2 transport in the blood ?
1) dissolved CO2
2) Biarbonate
3) carbamino compounds
153
How significant is dissolved CO2?
what law does this follow?
Henry's law - however CO2 is 24 times more solluble than O2 (solubility being 0.067ml *Dl *mmHg.
As a RESULT, dissoleved CO2 plays a significant role on its carriage in that aprox 10% of CO2 of the gas in the blood is disolved
154
How is bicarbonate formed?
Is this found in the blood and/or plasma?
What are the differences in formation of HCO3 depending on what evirnment it is in ?
What happens to the products of HCO3 production ?
H2O+Co2 = H2CO3 = H+HCO3
It forms in both the plasma and the RBC. However, formation in the plasma is very slow, but it is much faster in the RBC due to the presence of Carbonic Anihydrase.
HCO3 will shift out of the cell, however, the H+ remains within the RBC. To prevent the pH within the RBC dropping, Cl- shifts into the cell. This is the cloride shift
155
What is the Gibbs-Donnan equilibrium?
This is the rule that determines the movement of Cl- into the RBC post formation of H+ ions in the formation of HCO3 (aka the cloride shift).
156
what is the haldane effect?
Explain
This is the fact that the deoxygenation of the blood increases its ability to carry CO2, while the presence of O2 in the pulmonary capillaries helps with the unloading of Co2.
This is due to the reduced form of Hb being less acidic (better acceptor of protons) compared to the non reduced form (T form - tense - ie bound to O2)
157
why are RBC larger in the periphery compared to the pulmonic circultion ?
The increased CO2 and cloride shift, make the RBC more osmolar, which draws in water, making them larger. They shrink in the periphery due to the loss of CO2 and the movement of CL out of the cell.
158
what are carbamino compounds?
this is CO2 that binds to amine terminals in blood proteins.
The most important is the globin protein of Hemoglobin which helps form carbaminohaemoglobin.
This represents about 30% of the CO2
159
What are useful anchor points when interpreting haemoglobin disassociation curve for alveolar capillary blood and mixed vnenous?
Pulmonary capillary
PO2 of100mmHg = SO2 97%
Mixed venous
PO2 of 40mmHg = SO2 75%
P50 = SO2 of 50% = Po2 of 27mmHg
160
how does the haldane effect explain the CO2 dissassociation curve?
this is more linear, however, the lower the saturation of Hb with O2, the larger the CO2 concentration for a given PCO2. Thus, as per haldane, the more reduced the Hb is, the better it is at mopping up H+ ions produced by carbonic acid disassociation and greater the ability faility of reduced Hb to form carbaminohemoglobin
161
what is the henderson-hasselback equation?
H2CO3 -> <- H+ HCO3
This , and the logarhythm of the result (numbers are so small log is used) gives a pH of 7.4
This is VERY tightly controlled with a range of 7.38 ->7.42
162
what controls the HCO3 concentraiton in the blood and what controls the PCO2?
HCO3 -> kidney
PCO2 -> pulmonary respiration
163
what is base excess?
And base deficit?
this is what happens when the HCO3 concentration is increased but the PCO2 does not change (ie the bicarb is a base, so we have excessive amounts )
Base deficit is the inverse, ie not enough HCO3 for the PO2
164
as a rough rule of thumb, what can base excess tell us on blood work?
Base excess >2 = metabolic alkalosis
Base excess <-2= Metabolic acidosis (AKA base defecit)
165
what is respiratory acidosis?
What can cause this?
What is the response to this?
Increase of PCO2 which reduces the HCO3/PCO2 ratio, thus depressing the pH.
Causes; hypoventilation, ventilation-perfusion missmatch
The kidney responds by increasing the amount of HCO3 moving the HCO3/PCO2 back to normal (however, the renal compensaiton is often not complete and there will still be some base excess)
166
what is respiratory alakalosis?
what causes it?
What are the responses to this?
This is when there is a decrease in PCO2 which increases the HCO3/PCO2 ratio.
This is caused by; hyperventilation, high altitude( which also causes hyperventilation)
Respiratory compensation is typically fast as the kidneys increase the secretion of bicarbonate (pee it out) and the respiratory center attempts to reduce the breathing rate.
167
what is an abnormally low PO2 in tissues called?
Why does this occur ?
Hypoxia
This is when the tissue PO2 drops bellow 3mmHG.
things that cause this are;
1) decreased O2 delivery to tissues (e.g. shock, embolus etc) [circulatory hypoxia]
2) reduced ability of the blood to carry O2
3) Reduced blood PO2 from pulmonary disease
4) toxin which interferes with the tissues ability to use O2 (histotoxic hypoxia -> cyanide)
168
why is the tissue PO2 lowest at the capillary interface?
this is to create a perfusion gradient for O2.
169
what is the innervation of the diaphragm?
phrenic nerve from spinal segments c3, c4 and c5
170
what is paradoxical diaphragmatic movement?
This is when one section of he diaphragm does not move (eg paralysis of a segment) and the whole diaphragm end up moving up rather than down during respiration
171
what is normal diaphragmatic movement during respiration ?
Moves down and pushes abdominal contents down and forward. During normal breathing the movement of the diaphragm is approx 1cm, but this can move up to 10cm during forced breathing
172
what is the innervation of the intervostal muscles?
What movement do they follow?
There are innervated by intercostal nerves that come off the spinal cord at T3, 4 and 5.
The muscles fibers are sloped downward and forward and when they contract they increase both the lateral and anteroposterior diameters of the thorax
173
During normal breathing, inspiration and expiration, which movement of the diaphragm and abdominal muscles are passive and active?
does this change when exercising or sick ?
Inspiration; diaphragm contracting and moving down is active, and abdominal muscle relaxation is passive
Expiration; Diaphragm relaxation and moving up is passive, while abdominal contraction is active. The chest wall contracting is also passive when at rest, however, this can become active during intense exercise.
174
What are the accessory muscles of inspiration ?
Scalene - elevates the first two ribs
Sternomastoids - elevate the sternum
These only really ever do anything during active breathing
175
How is inspiration and expiration assiseted during periods of intense exercise/sickness?
The abdominal muscles play a major role in pressuring the abdominal cavity (or depressurising) which helps the diaphragm move. the internal intercostals assist by pulling the ribs inward and downward (opposite of external intervostals) decreasing thoracic volume
176
what is hysteresis during breathing?
If you look the pressure-volume curve the expiratory pressure loop does not follow the inspiratory loop. This is because the lung pressure at any point in time during inspiration is higher than expiration. Also, the lung without any expanding pressure has some air inside it and the pressure around the lung is slightly higher than atmospheric pressure (airways close trapping air into the alveoli). This increases with age, as more air becomes trapped in the lung with some types of diease.
177
what is transpulmonary pressure and how can you determine this?
This is the difference in pressure between the alveoli (ie atmospheric) and outside of the lung. This is represented as 0 on the horizontal axis, thus, this can be used to determine the transpulmonary pressure
178
what is lung compliance and how is this calculated ?
Ability of the lung volume to increase per unit of pressure.
This is the slope of the pressure volume curve and is calculated as;
compliance= ∆V/∆P
Normal range is -5 to -10cmH20 with the human lungs compliance being 200ml*cmH20
179
How does compliance change with disease?
REDUCED COMPLIANCE; increase in fibrous tissue -> pulmonary fibrosis, actelectasis, alveolar oedema (prevents alveoli inflation) i.e. stiffer tissue, cannot gain as much volume per unit of pressure
INCREASED COMPLIANCE; Alterations in elastic tissue -> emphysema, and normal aging cause this
180
What histological feature allows a lung to be compliant ?
Abundant elastic tissue between the airways of the lung. However, it is not only the presence of the elastic tissue, but also strand arrangement, where they crisscross cross allowing for 3D expansion (if they were all aligned along one plane, the lung could only expand in one direction, reducing compliance)
181
Define surface tension;
Why does it occur?
Surface tension is the tendency of liquid surfaces at rest to shrink into the minimum surface area possible. Surface tension is what allows objects with a higher density than water such as razor blades and insects (e.g. water striders) to float on a water surface without becoming even partly submerged.
At liquid–air interfaces, surface tension results from the greater attraction of liquid molecules to each other (due to cohesion) than to the molecules in the air (due to adhesion).[citation needed]
There are two primary mechanisms in play.
1) One is an inward force on the surface molecules causing the liquid to contract.
2) Second is a tangential force parallel to the surface of the liquid. This tangential force is generally referred to as the surface tension. The net effect is the liquid behaves as if its surface were covered with a stretched elastic membrane
182
Define Laplace's law and how is this modified for the alveolus
P= 4T/r
P= pressure
T= Tension (surface tension)
r= radius
In a suspended vacuum (like outer space), where there are no surfaces, a fluid's surface tension pushes a liquid to form a bubble, as this gives it the smallest surface area for a given volume and thus the highest surface tension.
However, the alveolus has an inner lining with a charge, and as a result, the fluid coats the inner surface of the spherical alveolus. Due to this property, the numerator is changed from 4 to 2 in laplaces law
P=2T/r
183
why is surfactant important?
Without this, the surface tension of the fluid coating the aveoli would cause these to collapse so that the fluid can form a sphere and minimise its surface area. surfactant reduces the surface tension of the fluid in the alveoli
184
why is pulmonary oedema foamy?
oedema dilutes sulfactant, and air being forced into this combination forms bubles that are incapsulated by the phospholipids of the surfactant which stabilises them as bubbles in foam
185
what cells produce surfactant?
What is surfactant made of?
type II pneumocytes (the cuboidal ish ones - not the fried eggs, they are type I
Surfactant is made of phospholipids and dipalmitoyl phosphatidylcholine (DPPC). These are made form fatty acids.
186
Why are pulmonary emboli damaging to the region of the lung distal to where they lodge?
This depletes fatty acid delivery to the type II pneumocytes, which then cannot make surfactant, causing the alveoli to collapse. Initially they often can get enough oxygen just from diffusion and the oxygen carried by the intertwined network of capillaries
187
although both a dislodged ACDO and a PTE block venous blood flow to the lung, why do we not see symptoms with the ACDO dislodgement but we do with the PTE.
Pulmonary Thromboembolism (PTE):
Composition: A thrombus — fibrin, platelets, RBCs
Biologic Activity: Active surface that can stimulate inflammation, platelet activation, and vasoconstriction via thromboxane A2 and serotonin.
Potential for propagation: thrombi can grow, break off, and propagate further.
Embolized Vascular Occluder:
Composition: Synthetic, inert material (e.g., stainless steel, nitinol, polyester, hydrogel, or PTFE).
Biologic Activity: Biocompatible and non-thrombogenic (intentionally engineered that way).
Fixed size and structure: Not deformable or prone to fragmentation.
188
How does adding surfactant reduce surface tension of a fluid?
DPPC molecules are linear and have one hydrophobic end and one hydrophilic end. They align themselves on the surface forming a film (unknown how) so that the hydrophilic end faces the hidrophil and hydrophoc->hydrophobic. This is like lining magnets up so that the + faces the +, thus they repel each other. This reduces the surface tension, preventing the fluid from compressing itself.
Additionally, if the film is compressed by increased pressure, the repulsion force increases (just like trying to force two magnets together when the + and + are facing each other)
189
Why does pulmonary oedema affect breathing?
1) increases the distance oxygen has to travel through to get into the blood
- increased fluid in the aveolus
- and increased interstitial fluid
2) The oedema interrupts the film of surfactant, reducing the surface tension of the fluid, making it more likely for the alveoli to collapse
3) as respiration worsens, less CO2 diffuses out of the blood, affecting relaxation of haemoglobin and O2 binding
4) As CO2 builds up in the blood, acidosis forms, shifting the oxyhemoglobin dissociation curve to the right, decreasing haemoglobin's affinity for oxygen.
5) Hypoventilation can cause an increase in Paco2 in the alveolar capillary, causing vasoconstriction, leading to reduced flow and possibly causing VQ mismatch, especially in those who may be lying down and getting atelectasis/have effusions, further causing lung collapse.
6) Dilution of the surfactant increases surface tension, which not only promotes alveolus collapse, but it also increases the suction effect within the alveolus drawing out more fluid from the capillaries
190
What are the physiological advantages of surfactant?
1) low surface tension -> increases lung compliance -> reduces energy expenditure needed in respiration
2) stabilises the alveoli; as there are >500 million alveoli, ie tiny bubble like structures, without surfactant there would be a tendency for small ones to collapse and large ones to blow up
3) keep alveoli dry; increased surface tension (ie without surfactant) would increase suction effects pulling water out of the capillaries
191
What is alveolar interdependence ?
the alveoli are clusterd together in large units. This allows them to interlink allowing one to stabilise another. Thus, if one group has a tendency to expand, it will be resisted by the surrounding alveoli and parenchyma. Vice versa, if there is one group that has a tendency to collapse, this will be prevented by the expansion of the surrounding parenchyma.
This is an additional mechanism which offers alveoli stability in addition to surfactant
192
what changes in chest wall conformation occur with pneumothorax and why?
The chest wall springs out and becomes more barrel-like. The chest (extrapulmonary) pressure is sub-atmospheric, which allows the lungs to expand, but also pulls the walls of the chest in (as it is compliant). When air enters the chest cavity, it will equilibrate to atmospheric pressure, thus removing the inward suction on the chest walls.
193
Explain why a right-to-left shunt has high perfusion but no ventilation.
This is because the blood bypasses the lungs completely. Ventilation to the lungs is appropriate, and their perfusion is also appropriate. However, from the shunts perspective, the blood has not been ventilated as it bypassed the alveoli. This results in V=0. A V/Q=0 is a true shunt.
So you will get a V/Q mismatch even with a shunt, despite there not actually being a problem with the ventilation its self.
194
With changes in air flow, there are changes in flow patterns. What are these and describe them ?
1) normal breathing -> laminar flow
2) mild-moderate increase in breathing rate -> laminar with eddies forming at branch sites, causing a mild increase in flow disruption
3) at high breathing rates-> turbulent flow through the airway
195
How does Poiselle's law alter resistance when length is doubled and radius is halved, and mathematically why?
Doubling length, doubles resistance. Halving the radius increases resistance 16-fold.
This is because R= (8*n*l)/πr^4
The radius is to the power of 4, which results in a significant rise in resistance as the radius decreases.
196
What factors affect a gas or fluid's ability to form laminar or turbulent flow at a specific velocity?
What is the equation and explain the concept.
The Reynolds number
Re= 2rvd/η
r= radius
v= average velocity
d= density
η= viscosity
Because density and velocity are in the numerator, and viscosity denominator, the equation gives the ratio of inertial to viscous forces.
In straight smooth tubes, turbulence is probable when the reynolds number exceeds 2000
turbulence is most likely when to occur when the velocity of flow is high and tube diameter is large (for a given velocity [can swoosh around more])
197
what are the challenges in applying the concepts of the Reynolds number to the bronchial tree?
There are a lot of branches of different sizes and frequencies which can affect the flow profile. Reynolds is best applied to a straight tube.
If you have one large airway with a breakaway small airway, this is likely to form an eddie. This Eddie will travel down the airway for some distance before levelling out. Thus in the lungs, it is likely that laminar flow only truly occurs in the smallest airways where the reynolds numbers are very low
198
Why would turbulence in bigger airways be beneficial in the lungs?
Turbulent air flow will expose most of the air to the ciliary bodies and mucous making it easier to trap particles. If the air flow were truly laminar, then the center of flow would move faster, carrying the particulates down the airways, away from the filtering regions, quicker and just simply not exposing these to the cillia. It also helps humidify and warm the air
199
what is the site of maximum airway resistance in the lungs?
mid-size bronchi
larger airways are more turbulent but have larger radius
Small end bronchi have laminar flow
200
what controls the tone of the smooth muscle of the small airways and how does their diameter change airway resistance?
What are they types of receptor?
Vagus nerve controls motor innervation and thetone of the smooth muscle is under autonomic innervation.
Adrenergic stimulation -> bronchial dilation (need more O2 for fight and flight)
- as do isoproterenol and epinephrine
Parasympathetic activity -> bronchial constriction
- as does aceylcholine and a fall in PCO2 (direct effects on smooth muscle )
ß1 receptors -> principally in the heart
ß2 receptors -> principally in the smooth muscle of the bronchi/blood vessles/ uterus
201
how is the pattern of respiration generated and where in the brain is it controlled?
What modulates their control?
Pattern generator in the pons and medulla.
-> Medulla respiratory center; Pretz-Botzinger complex and dorsal respiratory group which are associated with inspiration, while the ventral respiratory group are associated with expiration.
The breathing cycle starts with no activity. Then over seconds there is ramping up of re repetitive bursts of action potentials which ramps up the inspiratory muscle activity. Then inspiratory action potentials cease, and the inspiratory muscle tone falls to pre-action potential levels.
Their control is modulated by the vagus and glossopharyngeal nerves which terminate in the tractus solitarius next to the inspiratory area
The expiratory area is quiescent during normal breathing. It becomes active during forceful breathing but there it is not known how it does that
202
How do you calculate the A-a gradient?
(PiO2 - PaCO2)/0.8
PiO2= (Patm – PH2O) x FiO2
203
what is the Apneusic center?
Area in the lower pons which. Impulses from this site ramp up the breathing action potentials and have general excitatory effects on apneic breathing
204
What is the pneumotaxic center ?
This is in the upper pons. Switches off or inhibits the respiratory centre. This is thought to fine tune the respiratory rhythm
205
what is the role of the cortex in breathing?
breathing is under voluntary control to a degree and the cortex can overide the brain stem within limits - Ie we can breath hold, hyperventilate etc.
Voluntary breath hypoventilation is more challenging as increased arterial PCO2 and low PO2 will allow the brain stem to overide the cortex - hence we cannot suffocate ourselves to death
206
what is the role of the hypothalamus in breathing?
the limbic system in the hypothalamus will affect breathing in response to emotional changes
207
what are central chemoreceptors?
ventral surface of the medulla in the vicinityof 9th and 10th CN. respond to change in H+ thus control breathing based on CSF pH
## Footnote
the are found just bellow the surface of the brainstem
208
what are peripheral chemoreceptors ?
carotid bodies, aortic body (above and bellow aortic arch). Respond to decreases in PO2 and pH, and increases in PCO2
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what receptors that control respiration are found in the lungs?
1) pulmonary stretch receptors
2) Irritant receptors
3) J receptors -> juctacapillary (respond quickly to chemical irritation resulting in rapid shallow breathing - the chemicals are those in the capillary circulation
4) bronchial C fibers -> respond quickly to chemicals injected into the bronchial circulation in a similar fashion to J
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outside of the lungs, what other receptors are there that control breathing ?>
1) nose and upper airay
2) joint and muscle
3) Gamma system (sense elongation of muscle spindles - diaphragm/intercostal muscles)
4) arterial baroreceptos
5) pain and temperature
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why is cough suppression rarely indicated in cats?
because this is not a major sign for most clinical diseases, except chronic bronchitis, where the goal should be to resolve the underlying condition
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what clases of antitussives are there, which are most effective, and which have proven clinical trials. Give examples of each
Non opiate -> Dextromethorphan
No trials and poor evidence
Opiate -> e.g. butorphanol, hydrocodone etc.
Only butorphanol has a clinical trial.
these drugs are seen as the most effective
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what opiate receptors are targeted by opiods for cough supression ?
K = butorphanol
Mu= hydrocodone, codine
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what has been proposed as the mechanism of action of cough supression by opiates ?
Mostly just the sedative effects reduce the cough
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what are important considerations for the use of codeine in cough supression?
- not well studied
- Potential for human abuse
only 4% of codein reaches systemic level so antitussive maybe due to metablites
- 1/10th as potent as morphine from an anlgesic perspective but same antitussive effect
- can cuase constipation and sedation
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What is hycodan and what are important facts about this medication
Hydrocodone -> codeine + homatropine (anticholinergic)
Homatropine helps with bronchodilation, however, it is mostly put in the drug to reduce the abuse potentia.
Active metabolite can be present for several hours.
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why is butorphanol not an ideal PO option?
has a very high first pass metabolism so high doses are needed to reach plasma concentration
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in which species are bronchidilators an important therapy and why ?
primary indication for bronchodilators is treatment of cats with bronchial inflammation, regardless of cause (e.g., allergic, infectious, or idiopathic bronchitis), in which bronchoconstriction can be a major feature of disease. Dogs with bronchial disease rarely develop clini cally apparent bronchoconstriction but may show clini cal improvement when given these drugs because of effects beyond bronchodilation.
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why may bronchiodilators be used in apsiration pneumonia?
apsiration is mainly an alveolar parenchymal disease, however, due to the inflammation it is not uncommon to have bronchio constriction
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how do bronchiodilators work ?
Give examples of drugs;
Most are ß2 AGOnists.
ß2-> Gs->PKA->adenylate cyclase-> cAMP -> smooth muscle RELAXATION
Also
- stabilisation of mast cell reducing mediator release
- increase mucocilliary clearance
Terbutaline -> act 6 to 8 hours. It may be injected subcutaneously or intravenously to relieve an acute episode of bronchoconstriction. It is also available in oral formulations.
Albuterol (called salbutamol in some countries) is similar to terbutaline. It can be given orally as a tablet or liquid up to four times daily
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why are methylxanthines used in the treatment of some respiratory conditions ?
methylxanthines relax bronchial smooth muscle and hence are known as bronchodilators. However, there is evidence that they have antiinflammatory effects, including possible enhancement of the activity of corti costeroids, which may occur at lower concentrations than those producing the bronchodilating effects
The cellular basis of action of the methylxanthines is still not completely understood. Theories include.
- adenosine receptor antagonis; in humans adenosine triggers bronchoconstriction in asthmatic individuals.-
- inhibition of phosphodiesterase types 3 and 4 (like pimobendan and sildenafil, although less specific). Phosphodiesterases catalyze the breakdown of cAMP and cGMP to inactive products
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If you are treating a patient with theophyline and owner is not appreciating a response, what option do you have in an attempt to improve therapy with theophyline?
Theophiline assays can be performed to determine is plasma level is sufficient.
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what are side effects of theophypine?
nausea, manifesting as anorexia.
Cardiac adverse effects include increased heart rate, increased myocardial contractility (mild), improved right and left systolic function, vasodi lation (mild), and diuretic effect (weak). At high doses (>100 mg/kg), cardiac arrhythmias are possible.
If the drug is injected intravenously, CNS effects are more likely because of rapid and high blood concentration
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when are glucocorticoids used for the treatment of respiratory disease?
treatment of other inflammatory respira tory diseases such as eosinophilic bronchopneumopathy, tracheobronchomalacia, and chronic (lymphoplasma cytic) rhinitis.
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How do glucocorticoids work in respiratory disease ? which inflammatory cell population do they not affect?
- bind to receptors on cells inhibiting the transcription of genes which produce inflammatory mediators (cytokines, chemokines, adhesion molecules) -> decrease in the synthesis of inflammatory mediators such as prostaglandins, leukotrienes, and plateletactivating factor.
- enhance the action of adrenergic agonists on β2receptors in the bronchial smooth muscle, either by modifying the receptor or augmenting muscle relaxation after a receptor has been bound. Corticosteroids prevent downregulation of β2receptors and may be synergistic when used with β2agonists.
They DO NOT affect mast cell function
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what kind of drug is fluticase and why does it not have significant systemic side effects?
Corticosterone
In people, fluticasone has a systemic absorption of only 18% to 26%, and there are extensive firstpass effects and high protein binding that prevents significant sys temic active blood concentrations if it is swallowed after delivery. Therefore, clinical effects are mostly confined to the airways, and the systemic action is minimized.
lthough there was some suppression of the hypothalamic pituitaryadrenal axis (indicating some systemic absorp tion), systemic effects on immune cells (lymphocytes and lymphocyte function) were not observed, which demon strated that inhaled flunisolide is capable of producing a local effect in the airways with minimal effects on the systemic immune system.
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how do expectorants work?
Examples of these?
enhanced clearance of bronchial exudate, and promotion of a more productive cough.
Mechanism of action for stimulation of mucous secretions is via a vagally medi ated reflex action on the gastric mucosa
Guanfensin increases mucosal production at high doses, however, most formulations of expectorant do not have a high enough dose for dogs and cats.
Most treatments result to nebulisation, maintaining hydration status and physical therapies such as cupage.
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what are important considerations when selecting an antimicrobial with pulmonary infection?
Give examples of approriate and not appropriate choices
Properties that favor penetra tion to the Epithelial lining fluid (EL) include high lipophilicity, high potency of the drug (low minimal inhibitory concentration), and the concentration of free (unbound) drug in the interstitial fluid.
Drugs such as macrolides (erythromycin, azithromy cin), tetracyclines, and fluoroquinolones appear to achieve adequate concentrations in ELF.
βlactam antibiotics, especially the highly protein bound drugs, and aminoglycosides do not reach high concentrations in the ELF but may diffuse into the interstitial space to achieve effective concentrations in the presence of infection.
Inflammation that occurs in pneumonia produces leakage of drugs into the ELF regardless of which drug is selected.
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what are the causes of Feline Upper Respiratory Tract Infections ?
Why are these challenging infectiouns to deal with?
Feline herpes- virus type 1 (FHV-1) and feline calicivirus (FCV) cause approximately 80% of all URIs in cats
Less commonly, the bacterial agents Chlamydophila felis, Bordetella bronchiseptica, Mycoplasma spp., and Streptococcus canis have been implicated in primary disease.
Respiratory pathogens have a synergistic effect, and there is increased likelihood that cats harbor multiple pathogens when clinically ill.
FHV-1 is an antigenically stable DNA virus, whereas FCV is an RNA virus with multiple strains of varying virulence. Both viruses maintain carrier states, both are readily spread by fomites, and droplets can be transmitted up to 5 ft by forceful sneezing.
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what is used in the diagnsosi of feline URI
Real-time polymerase chain reaction (RT-PCR) is one test used to evaluate potential infectious primary causes of URI. However, RT-PCR results must be interpreted with caution, especially in individual cases (test cannot distinguish between infection, commensal and vaccine). higher validity in group setting where 5-10 cats or 10% of the population should be tested.
Histo if died - esp if there is a multi-cat outbreak
Do not forget, signs cross over with other non infectious disease such as neoplasia, rhunitis, polyps etc.
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How to treat a cat URI ?
Most self-resolving within 2 weeks
Attempt a diagnosis as most are viral (abs will not help)
If bacterial;
Antibiotics are often administered to treat secondary bacterial infection or to target known or suspected primary or coinfecting bacteria. Doxycycline is commonly chosen to treat suspected infection with Bordetella, Chlamydophila, and Mycoplasma spp. Doxycycline (in particular doxycycline hyclate) should be compounded into a liquid form, since it has been linked to esophagitis and esophageal strictures in cats (or crush dry pills and mix with water). Treat for 5-7 day, unless chlamidiophila where 2-3 months tx is needed
Antivirals;
Lysine - essential amino acid which interfere with FHV replication
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what is canine infectious respiratory disease complex?
also known as kennel cough or canine infectious tracheobronchitis. Respiraory conditions which can be due to a variety of bacteria/viral causes. Often found in high population densities like shelters.
Most cases are viral in origin. Most common isolated include; canine herpesvirus (CHV), canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine parainfluenza virus (CPiV), canine respiratory coronavi- rus (CRCoV), and canine influenza virus (CIV).
Coinfections with multiple viruses and bacteria such as Mycoplasma spp., Bordetella bronchiseptica, and Strepto- coccus equi subspecies zooepidemicus are common and con- tribute to an increased severity of disease.
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how do you diagnose canine infectious respiratory disease complex?
Often not possible - each pathogen causes a similar spectrum of disease so picking an individual test is challenging.
Most dogs experience self-limiting disease. Attempts to obtain a causative diagnosis should be made when disease persists for longer than 7 to 10 days or is complicated by secondary bacterial pneumonia. Oropharyngeal, con- junctival, and nasal swabs or airway lavage specimens may be submitted for aerobic bacterial culture, for Myco- plasma culture, and for molecular diagnostic testing
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Some canine infectious respiratory disease complex cause specific signs. Give example;
-chorioretinitis in dogs with distemper
- footpad hyperkeratosis or chorioretinitis in distemper
-dendritic corneal ulceration in dogs infected with CHV
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how do you treat canine infectious respiratory disease complex?
usually self resolving although signs like cough may persist (esp bordetellosis 10->30 days). Cough supressants can be used in those with a NON non-productive cough
Young puppies (<6 to 8 weeks of age) should also be con- sidered candidates for early initiation of treatment, because disease may progress rapidly to pneumonia
primary or secondary bacterial infection, empiric treatment with amoxicillin/clavulanic acid or doxycycline could be considered. The optimal duration of treatment is unknown, but 7 to 10 days is a reasonable choice.
B. bronchiseptica bronchopneumonia may respond to a short course of treatment with nebulized aminoglycoside solutions (5 days of 3 to 5 mg/kg/day
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what pathogens which make up canine infectious respiratory disease complex can be prevented / minimised with a vaccine
B. bronchiseptica, CDV, CPiV, CAV-2, and CIV
Vaccines for canine transmissible respiratory disease are considered to be noncore vaccines, so they should be administered to dogs at risk of exposure, such as those that enter shelters, boarding kennels, shows, sporting competitions, popular dog parks, or pet daycare facilities.
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what are the most common causes of rhinitis in dogs?
How do you treat these?
he princi- pal diseases associated with chronic rhinitis are sinonasal neoplasia, idiopathic lymphoplasmacytic rhinitis, and fungal rhinitis
Nasal mites are uncommon
Mite; Ivermectin 0.2 mg/kg PO, with the dose repeated in 2 to 3 weeks.
fungal;
Aspergillus fumigatus is the most common cause of fungal rhinitis in dogs, but occasionally Penicil- lium spp., Rhinosporidium seeberi, and very rarely Crypto- coccus neoformans may cause disease in dogs. R. seeberi is associated with the growth of a granulomatous mass within the rostral nasal cavity
-> clotrimazole, voriconazole
Chronic rhinitis idiopathic
Doxycycline 3 to 5 mg/kg every 12 hours PO or azithromycin 5 mg/kg every 24 hours PO in com- bination with piroxicam 0.3 mg/kg every 24 hours PO is recommended, if systemic health allows use of a nonste- roidal agent. If distinct clinical improvement is observed in 4 to 8 weeks,
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