Respiratory Physiology Flashcards
1
Q
Explain the role of peripheral chemoreceptors in respiration. What are they are more responsive to?
A
o More responsive to changes in the oxygen content of blood but also respond to changes in pH and carbon dioxide.
o Carotid bodies: bilaterally @ bifurcation of common carotids; pass from Hering’s nerves to the glossopharyngeal nerves and onto the dorsal respiratory group
o Aortic bodies: @ aortic arch; pass from the vagus nerve to the dorsal respiratory group
o These bodies are constantly exposed to only arterial blood
2
Q
Based on the oxygen-hemoglobin dissociation curve, what is the PO2 when 50% of Hb is saturated?
A
PO2 at 27 mmHg when Hb 50% saturated (P50 = 27mmHg)
The oxygen dissociation curve plots the % saturation against the partial pressure of oxygen, and its contribution to the total oxygen content. This is an S shaped curve due to the alterations in hemoglobin’s affinity for oxygen in response to other physiologic factors such as pH and temperature.
A reduction of PO2 below 60 mm Hg causes a rapid decrease in amount of O2 bound to hemoglobin. However, diffusion of oxygen from hemoglobin to tissue cells is enhanced by this process.
The P50 represents the partial pressure at which hemoglobin is 50 percent saturated with oxygen. P50 provides a means of quantifying the hemoglobin’s affinity with oxygen and reflects the dissociation curves.
Right shift – hemoglobin has decreased affinity, increased P50 – takes more oxygen to reach 50% (higher partial pressure to get 50% saturated)
Left shift – increased affinity, decreased P50 – less oxygen to reach 50% (less partial pressure to get 50% saturated)
3
Q
Describe the cough reflex.
A
Bronchi and trachea are very sensitive to light touch (larynx and carina especially sensitive) Afferent signals pass from the respiratory passageways to the medulla by way of the vagus nerve. The initiates an influx of air and subsequent closure of the epiglottis and vocal folds to trap the air in the lungs. The abdominal muscles contract and forcefully expel the air.
4
Q
Describe the sneeze reflex.
A
Irritants in the nose send afferent signals to the medulla by way of CN V
5
Q
Describe what occurs with control of normal breathing (nervous control).
A
Normal quiet breathing is controlled by repetitive inspiratory signals from dorsal respiratory group transmitted to diaphragm; expiration is passive elastic recoil of lungs and thorax.
Dorsal respiratory group come from the IX and X CN.
6
Q
Describe when oxygen therapy will be effective in hypoxemia.
A
- 100% effective with decreased atmospheric oxygen
- Pretty effective (5x O2 delivery) with hypoventilation hypoxia
- Pretty effective with a decreased alveolar membrane diffusion because the increased PaO2 facilitates diffusion at a higher partial pressure
- Minimally effective in hypoxia caused by anemia, abnormal hemoglobin transport of oxygen, circulatory deficiency, or physiologic shunt
• Normal amounts of oxygen are already available to the alveoli • Small amount of increased O2 transport in the dissolved state may make a difference
5, Not effective in hypoxia caused by inadequate tissue use of oxygen
7
Q
Explain the dissociation of carbonic acids into bicarbonate and hydrogen ions.
A
Carbonic acid (in RBC, H2CO3) dissociates into hydrogen and bicarbonate ions (H+ and HCO3-) = Faster with carbonic anhydrase o About 70% CO2 transported to lungs from tissue • H+ combine with Hgb (powerful acid-base buffer)
8
Q
What ocurrs at the BBB with H+ and CO2 to stimulate respiration?
A
Effect of blood PCO2 in stimulating the chemosensitive area
- CO2 + H2O → carbonic acid → HCO3- + H+ → H+ after CO2 has diffused across BBB
- Chemosensitive region is stimulated much more rapidly if the CO2 enters via the CSF rather than the brain interstitial water (less protein buffers for the hydrogen in the CSF)
- The excitation of the respiratory center to the increased CO2 is great within the first few days but subsequently declines over the next 1-2 days
o Due to renal compensation for acidosis by retaining bicarb, AND bicarb diffusing across BBB to buffer H+ there
9
Q
How does alveolar ventilation occur?
A
• Alveolar ventilation: rate at which air reaches the gas-exchange regions
o The gas in the air really only goes down to the terminal bronchioles and not into the alveoli during normal inspiration. It makes it the rest of the way by simple diffusion.
10
Q
How does oxygen reversibly bind to hemoglobin?
A
O2 combines loosely/reversibly with heme portion of hemoglobin
o PO2 high = O2 binds to hemoglobulin (pulmonary capilaries)
o PO2 low = O2 is released (tissue capilaries)
11
Q
How many molecules of oxygen can be bound by 1 Hemoglobin?
A
4 molecules of Oxygen per 1 Hb
12
Q
Name 5 major categories of hypoxemia?
A
Extrinsic problems •
- Low FIO2 (high altitude) •
- Hypoventilation (neuromuscular disease) Pulmonary disease • 2. Hypoventilation (increased airway resistance, decreased lung compliance) •
- Diffusion impairment •
- V/Q mismatch o High V/Q: physiologic dead space o Low V/Q: physiologic R-L shunt Anatomic shunts •
- Right-to-left cardiac shunts Inadequate O2 transport to tissues •
- Anemia or abnormal Hgb •
- Hypovolemic shock Inadequate capability of the cells to use oxygen (uncoupling of oxidative phosphorylation) •
- Metabolic abnormalities, cyanide toxicity
13
Q
Name the 4 major factors that will shift the oxygen-hemogloblin dissociation curve to the right.
A
Situations when there is a decreased affinity of Hb to oxygen → Unloading of O2 (great in tissue)
- Increased PCO2
- Decreased pH (more acidic)
- Increased temp
- Increased 2,3-DPG (byporduct of glycolysis)
14
Q
Name the factors that can affect the oxygen-hemoglobin dissociation curve?
A
• pH Changes:
o Acidic (7.4 → 7.2): Shifts curve to right (about 15%)
o Basic (7.4 → 7.6): Shifts curve to left
- ↑ CO2 concentration → Shifts curve to right
- ↑ Blood Temperature → Shifts curve to right
- ↑ 2,3-biphosphoglycerate (BPG) → Shifts curve to right
o Phosphate compound in blood
15
Q
Parasympathetic stimulation to airways leads to ….
A
Bronchoconstriction via acetylcholine release (muscarinic)
16
Q
Sympathetic stimulation to airways leads to…..
A
Bronchodilation (B2 adrenergic)
17
Q
What are factors that affect the diffusion of gas through the respiratory membrane?
A
- Thickness of membrane (edema, fibrosis)
- Surface area of membrane (↓ by lung removal, emphysema)
- Diffusion coefficient of gas in membrane (CO2 20x faster than O2)
- Partial pressure difference of gas btwn 2 sides of membrane (PP> alveoli than in blood (O2)
Net diffusion from alveoli into blood
PP> blood (CO2), net diffusion from blood to alveoli)
18
Q
What are the effects of emphysema and pulmonary fibrosis on lung compliance?
A
Emphysema = Increased lung compliance (loss of elastic fibers) Pulmonary Fibrosis = Decreased lung compliance (increased stiffness of the lungs)
19
Q
What are the layers of the respiratory membrane?
A
o Layer of fluid lining alveolus (containing surfactant: surface tension of alveolar fluid)
o Alveolar epithelium composed of thin epithelial cells o Epithelial basement membrane
o Thin interstitial space btwn alveolar epithelium and capillary membrane
o Capillary basement membrane (fuses with alveolar epithelial basement membrane)
o Capillary endothelial membrane
20
Q
What are the main forms that CO2 travels in the body?
A
- Dissolved in solution
- Bicarbonate (Major form)
- Combined with hemogloblin (o CO2 reacts with water, amine radicals of Hgb → carbaminohemoglobin (CO2Hgb)
o Reversible reaction – slow!!
o Only small amount of CO2 reacts this way (1/4th quantity of Hgb)
o Carbamino + Hgb and plasma protein: 30% total amount transported
21
Q
What are the two extremes of V/Q mismatches?
A
Ventilation-perfusion ratio (V/Q): Respiratory exchange when imbalance btwn alveolar ventilation and alveolar blood flow
o No exchange f gases V/Q = 0 → Ventilation zero, yet there is still perfusion V/Q = infinity →Ventilation adequate, but zero perfusion
22
Q
What are the two qualities controlled in the inspiratory ramp?
A
- Rate of increase of ramp signal
- Limiting point at which ramp stomp sudddenly decreases
Rate of increase of ramp signal - during heavy respiration, ramp increases rapidly, fills the lungs rapidly
Limiting point of ramp cessation - earlier ramp ceases the shorter the duration of inspiration – and ultimately, increases respiration frequency.
Ramp - weak and stead increase of action potential to inspirator muscle, then ceases.
23
Q
What controls the mechanism of pulmonary hypoxic vasconstriction?
A
Direct action of alveolar PO2 on the vascular smooth muscle of pulmonary arterioles
HYPOXIC pulmonary vasoconstriction (HPV) is a reflex contraction of vascular smooth muscle in the pulmonary circulation in response to low regional partial pressure of oxygen (Po2). This vasoconstriction by the pulmonary vasculature represents its fundamental difference from the systemic circulation, which typically vasodilates in response to hypoxia.
24
Q
What determines tissue PO2?
A
Tissue PO2 determined by rate of O2 transport to tissue in blood and rate at which O2 is used by tissues
25
What does the sigmoidal shape of the oxygen-hemoglobin curve reflect?
Increased affinity for each successive molecule of O2 that is bound
26
What drives the mechanism for hypoxic pulmonary vasoconstriction?
a. Central chemoreceptors detect low arterial PO2 --\> systemic catecholamines --\> constriction of smooth muscles in small arterioles of hypoxic region
b. Central chemoreceptors detect low arterial PO2 --\> systemic vasoactive substances (nitric oxide, endothelin-1) --\> constriction of smooth muscles in small arterioles of hypoxic region
c. Low alveolar PO2 causes changes in local perivascular tissue --\> local catecholamines --\> constriction of smooth muscles in small arterioles of hypoxic region
d. Low alveolar PO2 causes changes in local perivascular tissue --\> local vasoactive substances (nitric oxide, endothelin-1) --\> constriction of smooth muscles in small arterioles of hypoxic region
D. Low alveolar PO2 causes changes in local perivascular tissue --\> local vasoactive substances (nitric oxide, endothelin-1) --\> constriction of smooth muscles in small arterioles of hypoxic region
Everything here happens locally. Get clinical improvement with inhibitors of NO synthase and blockers of endothelin receptors.
27
What effect does anemia have on the O2 saturation curve?
a. Shifts it upwards
b. Shifts it downwards
c. Shifts it to the left
d. Shifts it to the right
B = Shifts it downward - there is less oxygen carrying capacity in the blood overall, therefore at ALL PO2 values along the x axis will not pick up as much O2, so the O2 concentration on the y axis is lower. See the attached pic.
Upward shift caused by Polycythemia (opposite of anemia) - Increased oxygen carrying capacity overall.
* Right shift caused by increased H+, increased PCo2, increased temp- aka all the things that increase with exercise. Also increased 2,3 DPG with chronic hypoxia, high altitude, chronic lung diz. Right shift = increased unloading at peripheral tissues.
* Left shift caused by low H+, low PCO2, low temp. Also low 2,3 DPG from prolonged storage in blood bank. Left shift = increased uptake at lungs.
28
What graph is used to assess the compliance of the lungs?
Pressure-volume loops - The slope of each line is the compliance of the lung itself
29
What happens in the peripheral chemoreceptors when O2 falls below 60 mmHg?
When the pO2 falls below 60 mm Hg, nerve impulses from the carotid body increase rapidly and respiration increases
1. Stimulation by low PO2 may occur via glomus cells in bodies → synapse with nerve endings (or may be direct sensitivity of nerve endings to O2)
2. Increased CO2 and H+ also activate chemoreceptors; this effect is much less in magnitude than their direct effect, but occurs more rapidly
30
What happens when there is left shift in the oxygen-hemogloblin dissociation curve?
There is an increased affinity of Hb to oxygen → Harder to unload O2 (great in lungs)
31
What is Cheyne-Stokes breathing?
o Characterized by slowly waxing and waning respiration, occurring over and over again about every 40-60 secs o The basic cause is due to transient overbreathing: 1. Blow off too much CO2 → delay before changed pulmonary blood can be transported to brain and inhibit excess ventilation 2. When overventilated blood eventually reaches the brain, the center becomes depressed an excessive amount → CO2 increases in alveoli → again takes brain delay before it catches up
32
What is expiratory reserve volume?
Expiratory reserve volume → extra amount of air that can be expired by forceful expiration after the end of a normal tidal expiration
33
What is functional residual capacity?
Functional residual capacity → expiratory reserve volume + residual volume • This is the amount of air that remains after normal expiration.
34
What is inspiratory capacity?
Inspiratory capacity → equals the tidal volume + inspiratory reserve volume • The amount of air a person can breathe beginning at the normal expiratory level and distending the lungs to the maximum amount.
35
What is inspiratory reserve volume?
Inspiratory reserve volume → extra volume of air that can be inspired over and above the normal tidal volume
36
What is residual volume?
Residual volume → volume of air remaining in the lungs after the most forceful expiration
37
What is surfactant?
Used to greatly reduce surface tension, is produced by Type II alveolar epithelial cells (pneumocytes).
38
What is the Bohr Effect in regards to the oxygen-hemoglobin dissociation curve?
Shift of curve to right (due to ↑ CO2 or ↑ Hydrogen ions)→ Significant enhancement of release of O2 from blood into tissues, enhancing oxygenation of blood in lungs → Bohr Effect o Blood passes through tissue: CO2 diffuses from tissue cells to blood → ↑ blood PCO2 → ↑ blood H2CO3 (carbonic acid) and hydrogen ions → Shifts curve to right and downward → forcing O2 away from Hgb and thus delivering ↑ O2 to tissues o Lungs: CO2 diffuses from blood into alveoli → ¯ blood PCO2 → ¯ hydrogen ions → Shifts curve to left and upward → Greater binding of O2 to Hgb at any given alveolar PO2
39
What is the chloride shift in RBCs?
• Many ions diffuse from RBCs into plasma (Cl takes their place in RBCs = bicarbonate-chloride carrier protein → 2 ions in opposite directions o Cl content of RBCs greater in venous than arterial RBCs → Chloride Shift (phenomenon)
40
What is the difference between anatomic and physiologic dead space?
• Physiological dead space → equal to the number of alveoli not participating in gas exchange • Anatomic dead space → refers solely to those airways not participating in gas exchange whereas physiologic dead space is equal to the anatomic dead space plus the non-functional alveoli (anatomic and physiologic dead space or nearly equal in healthy patients)
41
What is the equation for forming bicarbonate from CO2?
CO2 + H2O → (carbonic anhydrase) H2CO3 → H+ + HCO3-
42
What is the function of the nose?
Air is warmed, humidified, and filtered. Turbulent filtration occurs as the air hits the turbinates and must change direction
43
What is the greatest resistance to passage of air in a normal patient?
The resistance of the large airways
44
What is the Haldane Effect?
o ↑ CO2 in blood causes O2 to be displaced from Hgb (Bohr effect) o Important factor for ↑ O2 transport o Opposite true: Binding of O2 with Hgb tends to displace CO2 from blood (Haldane effect) More important at promoting CO2 transport than the Borh effect is at promoting O2 transport Combination of O2 with Hgb in lungs causes Hgb to become a stronger acid • Displaced CO2 from blood into alveoli: 1. More highly acidic Hgb has less tendency to combine with CO2 to form carbaminohemoglobin (displacing more CO2 that is present in carbamino form in blood) 2. ↑ Acidity of Hgb causes release of excess Hydrogen ions and binds with bicarbonate to form carbonic acid (dissociated in water and CO2 and CO2 is releases from blood into alveoli into air)
45
What is the Hering-Breuer inflation reflex?
o Lung inflation signals limit inspiration (Hering-Breuer inflation reflex) Stretch receptors in the lungs transmit signals via the vagus nerve to the dorsal respiratory group to limit inspiration when the lungs are full of air Similar to the pneumotaxic center in that it switches off the inspiratory ramp = inhibits inspiration (but increases the respiratory rate) when the lungs are full
46
What is the intrapleural pressure?
It is negative pressure (opposing forces of the lung trying to collapse and the chest wall trying to expand
47
What is the most important component of surfactant?
DPPC (dipalmitoyl phosphatidylcholine) - based on amphipathic nature of phospholipid (hydrophobic on one end and hydrophilic on the other end) - Reduces surface tension depsite small radius on alveoli
48
What is the normal direction of fluid flow in the pulmonary capillaries?
The normal outward forces of the capillary are just slightly greater than the inward force and so fluid constantly leaks into the interstitium (pumped back into circulation through lymphatics through slight negative interstitial pressure)
49
What is the oxygen-hemoglobin dissociation curve?
↑ % Hemoglobin bound as PO2 ↑ = percent saturation of hemoglobin o When PO2 = 95 mmHg → 97% bound to Hgb o When PO2 = 40 mmHg (tissues) → 75% bound to Hgb
50
What is the rate of alveolar ventilation?
Alveolar ventilation per minute is the total amount of new air entering the alveoli per minute. It is equal to the amount of new air that enters the alveoli X the respiratory rate (Va=RR X (Vt-Vd)) • Vd = dead space • Vt = tidal volume
51
What is the result of histamine in the airways?
Bronchiole constrictions (works locally)
52
What is the role of CO2 in controlling respiration?
Excess carbon dioxide or H+ ions → stimulate the respiratory center directly to increase strength of inspiration and expiration • Hydrogen ions are the only important stimulus for the chemosensitive area • However, H+ do not readily cross the BBB or Blood-CHSF barrier; thus CO2 ends up being more important
53
What is the role of hemogloblin in oxygen transport?
• 97% O2 carried on hemoglobin in RBCs • 3% O2 dissolved in water in plasma and blood cells
54
What is the role of O2 in controlling respiration?
Oxygen → no direct effect on respiratory center; acts on peripheral chemoreceptors in carotid and aortic bodies → signals to respiratory center
55
What is tidal breathing?
Tidal volume → volume inspired or expired with each normal breath
56
What is total lung capacity?
Total lung capacity →Equals the vital capacity + residual volume • Maximal volume to which the lungs can be expanded with the greatest possible inspiratory effort
57
What is typically the percent saturation of systemic arterial blood?
97% (95 mmHg)
58
What is typically the percent saturation of venous blood?
75% (40 mmHg)
59
What is vital capacity?
Vital capacity → inspiratory reserve volume + tidal volume + expiratory reserve volume • This is the maximum amount of air a person can expel from the lungs after first filling the lungs to their maximal extent and then expiring to their maximal extent
60
What Law governs the diffsuion of O2 and CO2 across membranes?
Fick's Law of Diffusion (driven by partial pressures difference of the gas)
61
What occurs in automatic control of pulmonary blood flow distribution?
Decreased oxygen concentration in the alveoli (less than 73 mmHg PO2) results in vasoconstriction of the surrounding vessels →shunting blood away from the hypoxic alveoli. • This is the opposite of what occurs in the other vascular beds
62
What stimulates ventilation during exercise?
Chemical signals ARE NOT the stimulus for increased respiration during exercise (they are normal!) 1, Instead, brain higher functions send collateral messages to the respiratory centers (while they are sending messages to muscles to stimulate contraction) 2. Movements of the limbs stimulates joint and muscles proprioceptive receptors that transmit impulses to the DRG to stimulate ventilation
63
Where is carbonic anyhdrase found in high concentrations?
In RBCs Aids in transport of CO2 in blood
64
Where is the expiratory center in brain?
Ventral respiratory center
65
Where is the inspiratory center in brain?
Dorsal respiratory center
66
Why does administration of 100% oxygen NOT improve hypoxemia during shunting?
a. Worsens vasoconstriction + shunting, therefore worsening the degree of shunting in the lungs
b. Not true - it DOES improve hypoxemia during shunting.
c. Depresses respiratory drive, causing decreased respiratory rate and worsening hypoxemia
d. The shunted blood does not get exposed to ventilated alveoli and the blood exposed to ventilated alveoli is already saturated.
D .. Usually increases respiratory drive because the chemoreceptors detect increased arterial PCO2 from the shunted blood and icnrease the ventilation. This lowers PCO2 but has no effect on the PO2.
67
What is vital capacity?
The exhaled volume after a maximal inspiration
68
What is tidal volume?
The amount of air entering the lung while breathing
69
What is residual volume?
The gas remaining in the lung after a maximal expiration
70
What is the functional residual capacity?
The volume of gas in the lung after a normal expiration
71
What is the alveolar ventilation?
The volume remaining in the anatomic dead space. It represents the amount of fresh inspired air available for gas exchange. \*Anatomic dead space is the volume of the conducting airways (where no gas exchange occurs)
72
What is total ventilation?
The total volume leaving the lung each minute. Can be measured = (tidal volume x respiratory frequency )
73
What is called recruitment?
It’s the opening of vessels and conduction of blood through these vessels to lower overall vascular resistance. This happens when there is a rise in the pulmonary arterial or venous pressure.
74
What is called distension?
Is the increase in caliber of the capillaries when there is an increase in vascular pressure. Often occurs together with recruitment.
75
What effect do drugs like serotonin, histamine and norepinephrine (drugs that cause muscle contraction) have on the pulmonary vascular resistance?
They increase pulmonary vascular resistance. They are potent vasoconstrictors, specially when lung volume is low. This is due to the role of smooth muscle in determining extra-alveolar vessels caliber.
76
What is Zone 1 and when does it occur?
The region at the top of the lung when pressure falls below alveolar pressure impeding blood flow, therefore it becomes in alveolar dead space (it is ventilated but unperfused lung). This only occurs when pressures are significantly reduced (after severe hemorrhage) or if alveolar pressures are raised (during positive pressure ventilation).
77
When diagnosing RAO, hyperresonance may be detected upon thoracic percussion. This indicates that:
a. Alveoli are more distended because increased bronchoconstriction keeps air trapped in them
b. The horse has emphysema
c. Bronchioles are more distended because increased bronchodilation keeps air trapped in them
d. Alveoli have ruptured
a. Alveoli are more distended because increased bronchoconstriction keeps air trapped in them
78
The volume of air in a normal breath is called:
a) Total lung capacity
b) Vital capacity
c) Tidal volume
d) Residual volume
c) Tidal volume
79
The primary chemical stimulus for breathing is the concentration of:
a) Carbon monoxide in the blood
b) Carbon dioxide in the blood
c) Oxygen in the blood
d) Carbonic acid in the blood
b) Carbon dioxide in the blood
80
Which are three important Gram (-) bacteria that are part of the bovine respiratory disease complex?
a) Mycoplasma bovis, Mannheimia haemolytica and Pasteurella multocida
b) Mannheimia haemolytica, Pasteurella multocida and Histophilus somni
c) Mycoplasma bovis, Histophilus somni and Streptococcus sp.
d) Trueperella Pyogenes, Mannheimia haemolytica and Pasteurella multocida
b) Mannheimia haemolytica, Pasteurella multocida and Histophilus somni All a concern for endotoxemia, Gram (-) aerobic bacteria
81
Which of the following does not shift the oxygen dissociation curve to the right?
a. Acidemia
b. Hypercapnia
c. Hypothermia
d. Increased 2,3-diphosphoglycerate
c. Hypothermia
82
The definition of Functional Residual Capacity is:
a. The volume of air remaining in the lungs after maximum exhalation
b. The volume of air in the lungs at the end-expiratory tidal position.
c. The maximum volume of air that can be exhaled from resting end-expiratory tidal position.
d. The maximum volume of air exhaled from the maximum inspiratory level.
b. The volume of air in the lungs at the end-expiratory tidal position.
83
Which of the following will shift the oxygen-hemoglobin saturation curve to the right?
a. Increased pH
b. Decreased temperature
c. Decreased CO2
d. Increase 2,3-biphosphoglycerate
d. Increase 2,3-biphosphoglycerate
The production of 2,3-BPG is likely an important adaptive mechanism (it increases for several conditions). It increases in the presence of diminished peripheral tissue O2 availability, such as hypoxaemia, chronic lung disease, anaemia, and congestive heart failure, among others. High levels of 2,3-BPG shift the curve to the right , while low levels of 2,3-BPG cause a leftward shift, seen in states such as septic shock, and hypophosphataemia.
84
The primary secretagogue stimulating secretion of mucins in the normal airway is:
a. Histamine
b. ATP
c. Acetylcholine
d. Serotoni
b. ATP
85
Effects of alveolar hypoxia
vasoconstriction
86
Hypoventilation is due to which acid base disturbance?
Metabolic alkalosis
87
Pulse oxymeter at 90
60 mmHg
88
SaO2 of 90% corresponds to _____ mmHg
60 mmHg
89
Blood gas changes in a V/Q mismatch ©
V/Q = 0 --\> same as venous blood (PO2=40; CO2=45)
V/Q = infinity --\> same as inspired air (PO2=149; CO2=0)
90
Why is mechanical ventilation challenging in cases of ARDS/ALI?
Areas of mismatch with areas of normal lung tissue
Predisposes to ventilator-induced lung injury
91
PaO2/FiO2 ratios to classify ARDS/ALI
\< 300 mmHg ALI (PaO2 \< 63)
\< 200 mmHg ARDS (PaO2 \< 42)
92
How would you institute ventilation in a case of ALI/ARDS?
Low tidal volumes
93
Would you use bronchodilators to treat a case of ALI/ARDS?
No! It can worsen the V/Q mismatch
95
What are the principals hallmarks of ALI/ARDS?
1. Increased alveolar-capillary permeability edema\*
2. Infiltration and activation of inflammatory cells
3. Atelectasis
4. Pulmonary hypertension
96
Clinical effects of ALI/ARDS
* Dyspnea
* Profound hypoxemia secondary to V/Q mismatch
* Reduced lung compliance
97
Important diagnostic test in ALI/ARDS for confirming condition and assess progression
Serial measurements of PaO2
98
What is the mainsted treatment for interstitial pneumonia?
Corticosteroids
Early and agressive therapy provides the best long-term outcome
99
What are the 2 most important factors influencing amount of O2 in blood?
1. Amount/concentration of hemoglobin in blood
2. % of Hb that is saturated with oxygen (SaO2)
100
What are 5 conditions that oxygen should be supplemented?
1. Hypoxemia (SaO2 \< 90%)
2. Hypotension (\< 18)
5. Respiratory Distress (RR\>24)
101
Under what conditions are SaO2 and PaO2 within normal limits, but tissue hypoxia present?
Low cardiac output, anemia, failure of tissues to use oxygen.
In these situations mixed venous oxygen (PvO2) better measure of tissue oxygenation
102
What is the gold standard for determining if oxygen supplementaion is needed?
Arterial PO2; Needed if \<80mmHg
103
What does a venous PO2 value indicate?
Influenced by amount of oxygen in arterial blood, tissue perfusion, uptake of oxygen (oxygen extraction ratio).
If \< 30mmHg = Low arterial oxygen OR high oxygen extraction ratio
104
What does a PEEP valve do to pulmonary capacity?
PEEP (positive end-expiratory pressure) valve = increases pulmonary functional residual capacity = Decreased work of breathing.
Recommended when there is a V/Q mismatch (pulmonary edema, hemorrhage, or parenchymal dz).
Leaves air in the lungs a little longer = increasing time for gas exchange.
Aimed at 5-10 mmHg (since 15 mmHg = Barotrauma!)
105
Name 7 ways that oxygen can be supplemented.
1. Flow By
2. Oxygen Hood
3. Oxygen Collar
4. Nasal Cannula
5. Nasal Catheters (nasal, nasopharyngeal, or nasotracheal)
6. Transtracheal catheters
7. Oxygen Cages
106
What are the 3 methods to assess supplemental oxygen effectiveness?
1. Clinical Evaluation (CS, lactate, ECG/Echo)
2. Pulse Oximetry (Bad if 65 mmHg)
107
What does pulse oximetry measure?
Peak oxygen saturation of Hb in capillary blood
108
What is the major burdens of massive PTE?
Mechanical Obstruction Exacerbated by hypoxia-induced vasoconstriction, release of hormonal substances from activated platelets on surface of thrombus
109
What is regional oligemia?
Hypovascular lung regions Appear as areas of increased radiolucency = reduced vascular filling distal to thrombotic occlusion
110
How are d-dimers formed?
Firbin Degradation Product: Formed when cross-linked fibrin is proteolyzed by plasmin Specific for active coagulation and fibrinolysis
111
What is the T1/2 of d-dimers?
About 5 hours, thus only good for detecting acute changes
112
What is the goal of anticoagulants in PTE?
Do NOT lyse the existing thrombus, instead inhibit propagation and prevent recurrent venous thrombosis
113
Name other diseases in which elevation in d-dimers has been noted.
1. Neoplasia
2. Hepatic dz
3. Renal failure
4. Cardiac failure
5. Internal hemorrhage
6. DIC
7. Following sx
114
What is the primary mechanism of unfractionated heparin?
Composed of mucopolysaccharides of varying weights Primary MOA is AT-III activity leading to inactivation of thrombin, Xa, IXa, XIa, XIIa (thrombin and Xa are most responsive)
115
How is low molecular weight heparin monitored?
Anti-Xa assay (since little anti-Iia activity - PTT cannot be used to monitor)
116
What are anti-platelet drugs?
Inhibit platelet aggregation = Preventing formation of primary platelet plug
117
Why are anti-platelet used used for arterial thrombi?
Arterial thrombi have a large platelet component compared to venous thrombi
118
Why are anti-platelet drugs recommended in PTE?
Even though these are venous thrombi (less platelets), in the early stages there is platelet acitvation that resutls in the release of mediators (release of serotonin, ADP, thromboxane A2) that can result in bronhconstriction, vasoconstriction, pulmonary hypertension
119
What is the MOA of aspirin, describe the low dosing of this medication?
COX inhibitor, prevents formation of prostaglandins including thromboxane A2 (made by platelets, COX-1, induces platelet aggregation), and prostacyclin PGI2 (produced by endothelial cells, COX-1 and COX-2 derived, inhibits platelet aggregation) § Irreversible, rapid, saturable antiplatelet effects § 50x greater COX-1 than COX-2 effects – so need ultra low dose to only inhibit TXA2 and not PGI2
120
What is the MOA of clopidogrel?
Inhibit ADP-induced platelet aggregation and so may work synergistically with aspirin (no effect on COX) = Irreversible!
121
What is thrombolysis and name 2 examples?
Plasminogen activators that result in production of plasmin = Dissolution of fibrin thrombus Streptokinase Tissue plasminogen activator (t-PA)
122
Describe the pathogenesis of pulmonary arterial hypertension.
Vasoproliferative and vasoconstrictive disorder Imblance btwn endothelium relaxinf factors (NO and porstacyclin) and endothelium constrictive factors (Endothelium-1, thromboxane, serotonin) = Increased vascular tone, endothelial smooth m proliferation, vascular remodeling, thrombosis
123
What are the 5 categories of pulmonary hypertension?
Based on the human Evian Classification
1. Pulmonary arterial hypertension (idiopathic, familial, condition associated with PH such as HW dz, shunts, drugs)
2. Pulmonary hypertnesion with left heart disease (most common in vet med)
3. Pulmonary hypertension associated with lung disease and/or hypoxemia (COPD, interstitial lung dz)
4. Pulmonary hypertension caused by chronic thrombotic or embloic dz (HW dz, neoplasia)
5. Other (Central pulmonary vein compression = lymphadenopathy, granulatmous dz, etc)
124
What is the most common cause of pulmonary hypertension in vet med?
Pulmonary hypertension with left heart disease (left sided myocardial dz or left sided valvular dz)
125
How can pulmonary hypertension be estimated with doppler echo?
If RV-RA systolic regurg (TR) can be quantified = Pulmonary arterial systolic pressure can be estimated § Use modified Bernoulli equation: 4 x V^2 = pressure (mmHg) § A TR jet of 2.8 M/sec or greater corresponds to an RV-RA gradient of 31 mmHg or greater (PA systolic hypertension) § Mild = 30-55 mmHg § Moderate = 6-79 mmHg § Severe = \>80 mmHg
126
What is the MOA of sildenafil?
• Phosphodiesterase-5 Inhibitors: Sildenafil (Viagra) inactivates cyclic AMP and GMP, second messengers of NO and prostacyclin, there is lots of PDE5 in the lung tissue versus other PDEs elsewhere in the body, so this is specific (mostly) for the lungs
127
What is the A-a gradient?
(A-a) O2 gradient = (PIO2 - 1.25 PaCO2) - PaO2 (A-a) O2 gradient = (150-1.25 PaCO2)-PaO2 • Values \< 15 mmHg = NORMAL • If gradient widen = Hypoxemia resulting from V:Q mistmatch • If the gradient is normal = Excludes pulmonary dz and suggests some form of central alveolar hypoventilation or abnormality in chest wall or inspiratory mm • Values \> 25 mmHg = ABNORMAL
128
What is key for colonization of the respiratory tract to result in pneumonia?
Bacterial adherence
129
Compare and contrast cardiogenic vs noncardiogenic pulmonary edema.
· Pulmonary edema → abnormal accumulation of fluid in extravascular spaces of lung (dynamic process) · Noncardiogenic pulmonary edema → ↑ vascular endothelial permeability rather than ↑vascular hydrostatic pressure (cardiogenic pulmonary edema) o ↑ vascular endothelial permeability due to injury to pulmonary microvascular endothelium (separates intravascular compartment from pulmonary interstitium and alveoli) o Unlike cardiogenic PE, ↑ permeability results in extravascular fluid with relatively high protein, leads to ↑ extravascular lung water content at low pulmonary hydrostatic pressures
130
Name causes of noncardiogenic pulmonary edema.
o Reflects primary pulmonary injury (aspiration of gastric content, near drowning, inhalation of smoke/toxic gas, blunt trauma, prolonged high inspired O2 contents) or systemic dz (sepsis, neurologic PE, pancreatitis, uremia, SIRS, pulmonary embolism)
131
What changes would you note on a arterial BG in noncardiogenic pulmonary edema?
· Arterial BG → pulmonary dysfunction (nonspecific), hypoxemia due to V-Q mismatch, PaCO2 low due to hyperventilation in response to pulmonary parenchymal disease o Later stages, ¯ pulmonary compliance (inability to ventilate → hypercapnia)
132
What structures are not included in the lung interstitium?
does NOT include the airspaces, the capillary endothelial cells, and the alveolar lining epithelium (but likely involves these structures)
???
133
Name 4 diseases that can result in pulmonary mineralization?
1. HAC
2. Pulmonary neoplasia
3. Idiopathic mineralization
4. Aging changes
134
What are the ways to classify a pneumothorax?
Traumatic vs spontaneous Open vs closed Simple vs tension
135
What are the 3 major risk factors of thrombosis?
1. Endothelial injury
2. Blood stasis
3. Alterations in blood constituents that favor thrombosis Known as Virchow's triad
136
What defines hypercaogulability?
1. Platelet hyperaggregability
2. Excessive activation
3. Decreased removal of coagulation factors
4. Deficiencies of natural anticoagulants (antithrombin and protein C)
5. Defective fibrinolysis
Acquired disorders in patients with underlying systemic dz known to be associated with an increase risk of thrombosis
137
Emboli in which part of circulation form PTE?
Venous Circulation = PTE
138
Name 4 pulmonary consequeneces of PTE.
1. Ventilation-perfusion mismatch
2. Bronchoconstriction
3. Hypoxemia
4. Hyperventilation Later
5. Regional loss of surfactant
6. Pulmonary infarction (rare) = Atelectasis, Edema, Effusion
139
What are the 2 forms that oxygen is carried in the blood?
1. Dissolved in arterial blood (responsible for diffusion pressure driving oxygen to tissue)
2. 97% attached to hemoglobin
140
What does a PaO2 with oxygen supplementation less than 65mmHg indicate?
Right to left shunt OR pulmonary dysfunction; Others (pneumothorax, severe hypovolemic shock, cardiogenic shock, obstructive airway disease)
141
What is CPAP?
Continuous positive airway pressure: Maintaining pressure above atmospheric pressure throughout respiratory cycle
142
What is a side effect of using PEEP?
Increased intrathroacic pressure = decreased venous return to heart and increase in dead space
143
What is a hyperbaric pressure?
Pressures higher than sea level
144
Why is the administration of high concentrations of oxygen bad?
Can result in oxygen toxicity - which can cause further lung injury
145
What are guidelines for ventilation?
1. Failure of Gas Exchange: PaCO2 above 50 mmHg PaO2 will not rise above 50 mmHg with test of 100% O2 or cannot be maintained with FiO2 0.6 or less
2. Need to assess the work of breathing in each patient = respiratory muscle exhaustion
146
What are the 2 classifications of patients that benefit from mechanical ventilation?
1. Primary pulmonary diseases (lung-injured patients) = Noncardiogenic and cardiogenic pulmonary edema, pneumonia, pulmonary contusions, ALI, ARDS, Airway obstruction, smoke inhalation
2. Neuromuscular Apparatus Failure (nonlung-injured patients) = polyradiculoneuritis (coonhound paralysis), myasthenia gravis, tick paralysis, botulism, tetanus, cranial cervical spinal cord lesions, brain injury, anesthetic complication, drug overdose, postcardiopulmonary resuscitation, respiratory muscle exhaustion caused by high work of breathing, diaphragmatic herniation, and chest wall trauma
147
What are the 5 main causes of hypoxemia?
1. Alveolar hypoventilation
2. V/Q Mismatch
3. Shunt
4. Low Insipired FiO2 (high altitudes)
5. Diffusion Impairment
148
What is the most common cause of hypoxemia?
V/Q Mismatch
149
What are the two ways that ventilators are cycled?
1. Volume-cycle (good for healthy lungs)
2. Pressure-cycle (good for injured lungs, but lots of variation in tidal volume delivered)
150
What are the 3 types of patient breaths in a ventilator?
1. Controlled breaths (set interval)
2. Assisted Breaths (patient can start it, ventilator finished it)
3. Spontaneous breaths (patient taking own breaths)
151
What is sensitivity of the ventilator?
Sensitivity - responsiveness of the ventilator to patient efforts to initiate breathing (assisted or spontaneous breaths)
152
What are the breath delivery mode of the ventilator?
1. A/C Mode: (Assist/Control) No spontanous breaths allowed (patients with poor respiratory drive)
2. SIMV Mode: (Synchronized intermittent mandatory ventilation): allows both mechanical and spontaneous breaths to be delivered according to patient demand
3. SPONT mode (spontaneous): the ventilator delivers no mandatory mechanical breaths. All breaths are spontaneous = Prewean mode
153
What are 4 ways that PEEP can improve ventilation?
1. increase in the functional residual capacity
2. alveolar recruitment
3. improved V/Q matching
4. redistribution of the extravascular lung water
154
What are 2 types of ventilator induced lung injury?
1. High pressures and use of high tidal volumes = Damage capillaries
2. Opening and closing of alveoli = Shear stress!
155
What is the trade-off of lung protective strategies for ventilation?
Hypoventilation (PaCO2 - 70-80 mmHg) permitted
156
Which type of patients are harder to keep sedate when using a ventilator?
lung-injured patients typically are more difficult to control because of high ventilatory drive from hypercarbia or hypoxemia
157
What is a potential cardiovascular cost of ventilation?
Declining cardiac output and resultant decreasing oxygen delivery = Eventually it outweighs the benefit of increasing arterial oxygen content
158
What is a potential sequela of ventilation?
Ventilator associated pneumonia (pathogenesis: colonization of the aerodigestive tract with pathogenic microbes early in the course of hospitalization and aspiration of the contaminated secretions)
159
What type of neurologic CS are possible in animals with nasopharyngeal disease?
Central nervous signs - if extension of fungus or neoplasia into brain Vestibular disease - if extension into tympanic bulla, opening of eustachian tube Horner's Syndrome (cats) - with invovlement of tympanie bullae Facial Nerve Dysfunction too (facial assymmetry and absent palpebral reflex)
160
Why is it important to determine if stertor vs stridor is present?
differentiate stertor (a snoring-type noise arising from the nasopharynx or pharynx, see effect of opening mouth with stertor) from stridor (a high-pitched noise arising from disturbance of air flow through the larynx or trachea)
161
What are the 2 main factors that need to be present to develop tracheal collapse?
1. Primary cartilage abnormality = Weakness of tracheal rings
2. Secondary factors capable of initiating progression to the symptomatic state
162
What is the primary defect responsible for intrinsic weakness of tracheal rings?
Reduction in the glycoprotein and glycosaminoglycan content of the hyaline cartilage of the tracheal rings = Reduced capacity of cartilage to retain water
163
Name potential factors that can contribute to clinical syndrome of tracheal collapse?
1. Cardiomegaly
2. Pulmonary Edema
3. Respiratory Infection
4. Upper Airway Obstruction
5. Chronic Bronchitis
6. Allergic Tracheobronchitis
7. Inhaled irritants (smoke)
8. Cervical trauma
9. Obseity
10. Tracheal intubation
11. HAC
164
When does collapse of cervical tracheal segment occur in?
Inspiration, decreased pressure within the trachea
165
When does collapse of the thoracic portion of trachea occur in?
Expiration, increased intrathoracic pressure
166
What creates the cycle of tracheal collapse?
• Once clinical signs are apparent, the syndrome is perpetuated by the cycle of chronic inflammation of the tracheal mucosa, which precipitates cough and in turn is exacerbated by the cough
○ Persistent inflammation of the tracheal mucosa leads to a loss of epithelium = fibrinous membrane formation = squamous metaplasia with polypoid proliferation evident in advanced cases
○ Population of ciliated cells is reduced significantly by the metaplastic changes in the mucosa, and the hyperplastic subepithelial glands secrete increasingly viscid mucus = normal ciliary function is replaced progressively by cough as the major tracheobronchial clearing mechanism
○ Once the condition becomes symptomatic, the changes in the dorsal membrane and cartilage are believed to progress beyond those of the original anatomic abnormality
167
What are the mainstays of treatment for tracheal collapse?
1. Management of Secondary Initiating Causes (weight reduction, CHF, inhaled irritatns, respiratory infections, collars) 2. Management of cough (antitussives, bronchodilators, glucocorticoids)
168
What is chronic bronchitis?
Inflammation (etiology unknown; environmental pollutants, secondhand smoke, or inhaled irritants) of conducting airways → chronic cough o Chronic, low-grade aspiration injury might play a role o Human Med: Role of bacterial infection in generation/exacerbation is widely debated (NOT established in dogs) o Disease of exclusion → tx based information from individual at controlling CS (NEVER cured!)
169
What are the goals of management in chronic bronchitis?
control inflammation (to limit CS); to diagnose/treat infection when it occurs; to prevent development of debilitating sequelae → bronchiectasis, cor pulmonale
170
Compare and constrast chronic bronchitis and asthma.
o 1. Chronic bronchitis: Inflammatory disorder of lower airways → daily cough, for which other causes of cough (including heartworm disease, pneumonia, lungworms, and neoplasia) are excluded 2. Asthma: Disorder of lower airways → airflow limitation (combo of airway inflammation, accumulated airway mucus, and airway smooth muscle contraction); Dramatic CS (acute wheeze and resp distress) or daily cough (humans: cough variant asthma); definitive dx based on pulmonary function tests
171
Briefly describe leukotrience production in relation to airway inflammation?
· Leukotrienes (inflammatory mediators from arachidonic acid → eicosanoids) o Cysteinyl leukotrienes: LTC4, LTD4, and LTE4 → Airway inflammation § Produce mucus hypersecretion, ↑ vascular permeability, ↑ mucosal edema; induce potent bronchoconstriction; chemoattractants to inflammatory cells (eosinophils, neutrophils)
