Pulmonary Physiology Flashcards
1
Q
Respiratory Physiology
Lung Volumes/Capacities:
Tidal volume (Vt):
A
~ 500 mL
Vt = volume in alveoli + volume in airways
2
Q
Respiratory Physiology
Lung Volumes/Capacities:
Inspiratory Reserve volume (IRV)
A
~ 3000 mL
Max volume inspired in addition to Vt
3
Q
Respiratory Physiology
Lung Volumes/Capacities:
Expiratory Reserve volume (ERV)
A
~ 1200 mL
Maximum forced expiration; volume expired below Vt
4
Q
Respiratory Physiology
Lung Volumes/Capacities:
Residual Volume (RV)
A
~ 1200 mL
Gas in lungs after max forced expiration; RV cannot be measured
5
Q
Lung Capacities Inspiratory Capacity (IC) =
A
Vt + IRV
6
Q
Lung Capacities
Functional Residual Capacity (FRC) =
A
ERV + RV
FRC: volume left over after normal Vt is expired, so aka “equilibrium volume”
7
Q
Lung Capacities Vital Capacity (VC) =
A
IC + ERV = Vt + IRV + ERV
a) Volume expired after maximal inspiration
b) VC ↑↑ w/chest size, male gender; ↓with age
8
Q
Lung Capacities
Total Lung Capacity (TLC) =
A
= VC + RV
9
Q
Lung Capacities
Recall, RV cannot be measured by?
A
Spirometry so the FRC and TLC cannot be measured by spirometry.
More interested in FRC; this is volume in lungs after normal tidal volume expiration (equilibrium volume).
10
Q
Lung Capacities
More interested in FRC; this is volume in lungs after normal tidal volume expiration (equilibrium volume).
Measure with?
A
Measure with He dilution/body plethysmography
11
Q
B.Lung Capacities
Dalton’s Law
A
Dalton’s Law - Px = (Total Pressure) x (% gas x in mixture)
12
Q
Dead Space:
Define:
A
Anatomic and Physiologic space that does not participate in gas exchange.
13
Q
Anatomic Dead Space:
Define:
A
Volume of the conducting airways/zone (nose, nasopharynx, trachea, bronchioles, terminal bronchioles).
1/3 of Vt (~500) = 150 mL; this fills the anatomic dead space and never sees gas exchange; the first air expired is unexchanged air - must sample end-expiratory air if interested in alveolar gasses.
14
Q
Dead Space
Estimate dead space with body weight
A
70 kg man ~ 150 lbs = 150 mL dead space
15
Q
Dead Space
Estimate during a breath:
A
(1) Inspiration of first breath (Vt ~ 500 mL), 350 makes it to alveolar sacs for gas exchange + 150 in anatomic dead space
(2) Expiration of first breath, 150 (unexchanged) anatomic dead space air is expired, but 150 mL of the 350 alveolar air (exchanged) replaces the anatomic dead space
(3) Inspiration of second breath, 350 makes it to the alveolar sac, but 150 of this air has already undergone gas exchange, so 200 mL is new exchangable air
16
Q
Physiologic Dead Space
Define:
A
Total volume of the lung that does not participate in gas exchange.
a)Physiologic Dead Space = anatomic dead space + functional dead space in alveoli (alveolar dead space)
17
Q
Physiologic Dead Space
Functional dead space occurs when?
A
Alveoli do not participate in gas exchange, or they do not ventilate.
(1) Normal alveoli are well perfused and ventilated
(2) This becomes important for shunting (blood goes to alveolus that is not ventilating, might as well be nothing).
18
Q
Physiologic Dead Space If perfusion (pulmonary blood flow) = ventilation?
A
Functional, physiological dead space is very low
Physiologic Dead Space ↑↑ if there is a ventilation/perfusion defect
19
Q
Dead Space Volume (VD) Calculation
Based on measuring?
A
Partial pressure of CO2 in mixed expired air, assuming that:
(1) All CO2 in expired air comes from functioning alveoli (ventilating and are perfused)
(2) No CO2 in inspired air
(3) No CO2 is added to mixed expired air from physiologic dead space (non-functioning alveoli + anatomical dead space)
20
Q
The air that does not see a functioning alveolus?
A
Will not see blood, therefore CO2 cannot be added to expired air from these anatomic/physiologic spaces.
21
Q
If dead space does not exist?
A
CO2 in expired air (PECO2) = CO2 in alveoli (PACO2) b/c all the CO2 in expired air represents
all the CO2 in alveoli coming from blood during gas exchange.
22
Q
The Equation: Volume Dead Space
A
(1) VD = Vt x (PACO2 - PECO2)/PACO2
(2) PACO2 cannot be measured directly, but because alveolar air exchanges with blood that will become systemic arterial blood, the PCO2 of arterial blood = PACO2
(3) Example: if 80% of alveolar CO2 is expired, the dilution factor=20%. Or, 20% of each Vt (.20xVt) is the dead space (=Vd)
(4) Example: if no dead space, all CO2 in alveoli is in expired air, and dilution factor =0. Or, 0% of each Vt (0xVt) = Vd = 0
23
Q
Ventilation Rate:
A
Volume of air in/out of lung per unit time
a) Minute ventilation = total volume moved in and out per time = Vt x #Breaths/min
b) Alveolar ventilation = total volume moved in/out per time corrected for the physiologic dead space
(1) Alveolar Ventilation = (Vt-Vd) x #Breaths/min
24
Q
Alveolar Ventilation Equation - inverse relationship between?
A
Alveolar ventilation and PACO2! ! ! ! !
25
Equation: alveolar CO2 equals amount of?
CO2 produced divided by Va (Ventilating aveolar).
a)This makes sense! The amount of alveolar CO2 ↑↑ w/↑CO2 production (exercise); likewise alveolar CO2 ↓↓ if ↑alveolar ventilation, b/c ↑CO2 is expired.
26
Alveolar Gas Equation - predicts
PAO2 (alveolar oxygen)
27
PO2 is determined by?
How much O2 enters (PIO2) and how much is removed (=CO2 produced = PACO2).
28
R = respiratory exchange ratio or respiratory quotient.
| Equation and Meaning?
R = CO2 produced/O2 consumption ~ 0.8
R = 0.8, meaning CO2 production < O2 consumption
Meaning, changes in alveolar ventilation affect O2 consumption more! Or, individuals have a CO2 production rate that is 80% of their oxygen consumption.
29
Example: What if R = 0.6?
| What is the rate of CO2 production, relative to O2 production?
(1) Rate of CO2 production ↓ relative to O2 production
| (2) PACO2/R will ↑, which will cause ↓PAO2
30
Forced Expiratory Volume
| Recall, vital capacity is volume?
Expired after maximum inspiration.
31
Forced vital capacity (FVC) is?
Total volume that can be forcibly expired after max inspiration.
32
FEV1 =
Volume forced out in 1 second.
33
FEV 3 =
Volume forced out in 3 seconds (no FEV 4 because entire vital capacity is expired forcibly in 3 seconds).
FEV3 = FVC
34
FEV1 and FVC (FEV3) are used for lung disease, specifically ratio?
FEV1/FVC
Normal: FEV1/FVC = 0.8
80% of forced expired air occurs in 1 sec
35
Obstructive lung disease (asthma) =
| What occurs to FEV1 and FVC?
Can’t get air out.
(1) Both FEV1 and FVC↓, but ↓↓FEV1 > ↓FVC
(2) Therefore, FEV1/FVC ↓
36
Restrictive lung disease (fibrosis) =
| What occurs to FEV1 and FVC?
Can’t get air in (max inspiration↓).
(1) Both FEV1 and FVC ↓, but ↓FEV1 < ↓↓FVC because max inspiration↓
(2) Therefore, FEV1/FVC ↑
37
Mechanics of Breathing
Muscles + Thoracic Cavity
Inhalation =
Contraction of diaphragm ↑dimensions of thorax = ↑volume of thorax and lungs
a) ↑Volume = ↓Pressure (Boyle’s Law)
b) ↓Pressure in lungs allows air to enter the conductive and respiratory zones.
38
Mechanics of Breathing
Muscles + Thoracic Cavity
Expiration =
Relaxation of diaphragm (usually passive process) = ↓volume of lungs = ↑pressure of lungs = air forced out.
39
Compliance
| Define:
Compliance = how much volume changes from pressure change.
| Inversely related to elastance.
40
Compliance
| Rubber band analogy:
a) Thicker vs. thinner rubber band = lots vs. little “elastic tissue”
(1) Thicker band (↑elastic tissue) has ↑recoil, but ↓stretchability = ↓compliance if ↑elastic tissue
(2) Thinner band (↓elastic tissue) has ↓recoil but ↑stretchability = ↑compliance if ↓elastic tissue.
41
Compliance
Lungs:
Diseases
↓Compliance =
Stiff lungs = restrIctive lung disease; can’t get air In! Fibrosis / ARDS.
42
Compliance
Lungs:
Diseases
↑Compliance =
Flabby lungs = Obstructive lung defect; can’t get air Out! Asthma / COPD.
43
Compliance of Lungs
| During inspiration:
The expanding pressure (negative ↓P from ↑thoracic volume) expands the lungs and ↑volume of lung air.
44
Compliance of Lungs
| As lung volume ↑ the alveoli?
The Alveoli become less compliant because they are elastic + relaxation of diaphragm allows expiration.
45
Hysteresis depends on?
Surface tension, which depends on liquid-liquid or
| liquid-air interfaces.
46
Liquid-air interfaces have?
Weak intermolecular forces, while liquid-liquid are very strong.
47
During inspiration, lung begins unexpanded and the liquid-liquid forces?
Must be overcome, therefore ↓compliance.
48
During expiration, lung begins expanded and there are no liquid-liquid forces?
To overcome, so ↑compliance
49
Compliance of Chest Wall
| Normally, intrapleural space has a?
Negative pressure because of two forces that “pull” and expand the space:
50
Chest wall naturally wants to?
Expand pull out --> ↑Volume = ↓Pressure.
51
Lungs are elastic and naturally want to?
“recoil” or collapse --> ↑Volume = ↓Pressure
***A nice cycle is formed by the creation of negative intrapleural pressure; this pressure allows air to fill the lungs (preventing natural collapsing of lungs) and chest to stay contained (preventing natural popping out of chest).
52
Pneumothorax occurs when?
Air enters the intrapleural space and becomes = Patm
| rather than negative.
53
Pneumothorax there is no negative pressure, so?
The balance and naturally tendency of lung and chest break down.
(a) Lungs collapse
(b) Chest pops out
54
Compliance of Lung and Chest Wall
| Individually, lung and chest wall have similar?
Compliances; together, the combined compliance is lower (two rubber bands are harder to stretch than each individually).
55
When volume = FRC, lung collapsing force = chest wall expanding force?
Combined lung/chest is content
56
When volume < FRC, lung collapsing/elastic force ↓↓ < chest wall expanding force?
Lung/chest want to expand
57
When volume > FRC, lung collapsing force ↑↑ > chest wall expanding force?
Lung/chest want to collapse
58
Think again of rubber bands: When left alone?
There is no tendency to stretch or recoil.
59
Think again of rubber bands: When forcibly recoiled?
The two rubber bands will want to stretch.
60
Think again of rubber bands: When forcibly stretched?
The two rubber bands will want to recoil.
61
Compliance of Lung in Disease States
| Emphysema =
Loss of elastic fibers in the lung = ↑compliance = ↓recoil/tendency for the lung wanting to collapse.
62
Emphysema
| Pressure volume curves:
Lung PV curve has ↑slope because ↑compliance, and thus for a given volume the collapsing force is less than normal
63
Emphysema patients will try and ↑volume to generate?
A normal collapsing force; want a ↑FRC
64
Emphysema have combined lung + chest wall system will intersect 0 pressure?
At a higher volume to maintain the balance of forces.
| Expanding force of chest is no longer equally balanced, and thus has a tendency to pop out.
65
Emphysema patients look?
Barrel-chested
66
Compliance of of Lung in Disease States
| Fibrosis =
Restrictive lung disease where tissue becomes stiffer = ↓compliance = ↑recoil/collapsing force.
67
Fibrosis
| Pressure volume curves:
Lung PV curve has ↓slope because ↓compliance; for a given volume, the collapsing force is greater than normal.
68
Fibrosis expanding force <
Collapsing force
69
Fibrosis have the combined lung + chest wall system will intersect 0 pressure?
At a lower volume; attempt to balance forces.
70
Surface Tension of Alveoli
| Small vs. large alveoli have?
Different tendencies to collapse because of different surface tensions.
71
Alveoli are lined with fluid and collapsing pressure explained by?
Laplace’s Law P = 2T/r
T = Surface Tension
P = Pressure
r = Radius
72
Smaller alveoli have ↑intermolecular fluid forces =
↑surface tension = ↑collapsing pressure
73
↑ surface tension = ↑collapsing pressure occurs because?
When ↓r, ↑interactions of liquid molecules = ↓r + ↑T = ↑P
74
Larger alveoli have ↑ ?
Weak fluid-air forces = ↓surface tension = ↓collapsing pressure
This means that Psmall >>>> Pbig ==== Small empties into big.
75
***Problem***: Small alveoli have tendency to collapse when they see an opening (airway), but are better because?
They contribute to a larger total surface area for gas exchange. Answer = surfactant.
76
Surfactant =
Phospholipids lining alveoli that ↓surface tension
77
Surfactant made by?
Type II Pneumocytes (alveolar cells)
78
Surfactant most important component is?
Dipalmitoyl phosphatidylcholine (DPPC) <--- amphipathic (hydrophobic + hydrophilic)
79
Surfactant
| Mechanism:
DPPC molecules align based on attractive -phobic and repelling -philic regions. They disrupt the intermolecular forces in a small alveolus, weakening T (surface tension) ---> ↓collapsing pressure
80
***Moreover: ↓radius (normally ↑pressure) but w/surfactant?
Actually concentrates p-lipids of surfactant, which helps ↓T
81
Surfactant: So Psmall is NOT > Pbig, because?
Small bubbles with surfactant have ↓T and ↓r (and ↓r=↑surfactant concentration)
This means that when emptying air, small bubbles (alveoli) will not pop = STABLE ALVEOLI.
↓Collapsing tendency or “recoil” = ↑compliance.
82
Neonatal Respiratory Distress Syndrome =
Hyaline Membrane Disease
83
Neonatal surfactant made at?
24 weeks gestation
84
Loss of surfactant =
↓compliance = can’t get air in = restrictive
85
Fetus with no surfactant has?
↓compliance of lungs and ↑tendency of alveoli to collapse -------- “atelectasis”
86
↑# of collapsed alveoli =
↓alveoli in gas exchange = hypoxemia
| Recall, w/out surfactant small alveoli are UNSTABLE and “Pop!” emptying protein (hyaline) into alveoli.
87
Airflow/Pressure/Resistance:
| Flow =
ΔPressure/Resistance -----> Q = ΔP/R or ΔP = QR
P = Pressure
R = resistance
Q = Flow
88
Recall: Poiseuille’s Law: ---->
R = µl/πr4
If radius is halved, resistance goes up by 16-fold!
***medium bronchi have ↑resistance; even though smaller-radius bronchi exist, smaller are in parallel and have a ↓total resistance
89
The Breathing Cycle
| Three phases =
rest --> inspiration --> expiration --> rest...
90
During rest
(1) alveolar pressure =
(2) Intrapleural pressure =
(3) Transmural Pressure =
(1) alveolar pressure = Patm = 0
(2) Intrapleural pressure = -5
(3) Transmural Pressure = +5 ---> expanding pressure allowing inspiration
91
During inspiration
(1) alveolar pressure first?
(2) Intrapleural pressure = -
(3) Transmural pressure =
(1) alveolar pressure first ↓ to -1 because of ↑volume from expansion
(2) Intrapleural pressure = -6.5
(3) Transmural pressure = +5.5 ---> expanding pressure still
92
Inspiration Continues
(1) alveolar pressure back to?
(2) intrapleural pressure =
(3) Transmural pressure =
(1) alveolar pressure back to 0 from adding air
(2) intrapleural pressure = -8
(3) Transmural pressure = +8 ---> expanding pressure still
93
Expiration (Letter D)
(1) Alveolar pressure?
(2) intrapleural pressure =
(3) Transmural pressure =
(1) Alveolar pressure positive because ↓volume with ↑elastic forces
(2) intrapleural pressure = -6.5
(3) Transmural pressure = +7.5
94
Consider forced expiration
| Forced expiration occurs when?
muscles ↑intrapleural pressure.
This will normally not collapse lungs because elastic recoil of alveoli will experience this ↑intrapleural pressure and translate that into ↑↑alveolar pressure
95
Consider forced expiration
| As long as alveolar pressure > intrapleural pressure
Nothing will collapse
96
Consider forced expiration
| In COPD, there is loss of elasticity from lung tissue and thus?
↑compliance
97
In a similar scenario of forced expiration, the lack of elastance in these fibers =
↑chance of collapsing airways
98
Physiologically, ↑intrapleural pressure > ↑alveolar pressure and trasmural pressure is negative =
Collapse!
| COPD patients expire with pursed lips slowly to keep airway pressure ↑
99
Henry’s Law:
Amount (concentration) of gas dissolved Cgas = Pgas x Solubility_gas
100
Fick’s Law:
```
Predict rate of transfer via diffusion Vx = DA/T (ΔP)
Vx = Diffusion
D = Constant
A = Area
T = Distance
P = Pressure
Driving force is the pressure gradient
```
101
Diffusivity α solubility ===== CO2 and O2?
CO2 is 20x more soluble than O2; at any given partial pressure, diffusion of CO2 >>>>> O2
102
Clinical Importance of CO2 is 20x more soluble than O2 in Emphysema
Alveoli destruction = ↓A = ↓Vx
103
Clinical Importance of CO2 is 20x more soluble than O2 in Fibrosis + Pulmonary Edema
↑thickness of alveolar membrane = ↑T = ↓Vx
104
Clinical Importance of CO2 is 20x more soluble than O2 in Exercise
↑perfusion of pulmonary capillaries = ↑A = ↑Vx
105
Two Forms of Oxygen in Blood
Dissolved (~2%)
| HbO2 (98%)
106
Oxygen in Blood
| Dissolved (~2%)
Part that contributes to / related to PO2
- Dissolved amount ~ 0.3 mL/100 mL blood
- Dissolved amount is inadequate O2 for delivery; need another form!
107
Oxygen in Blood
| HbO2 (98%)
Hb = four porphyrin+gobulin+Fe2+ rings that can bind 4x oxygen
- Normal human blood = 15 g Hb/100 mL blood
- Oxygen Content of Blood = 1.39 mL of Oxygen/g x 15 g/100 mL = 20.85!
- Correct for fact that 97.5% saturation of Hb ---> 20.60 mL (damn!)
108
Determining Amount of Oxygen Delivered to Tissues Each Cycle
| ↑PO2 =
↑% Saturation
109
Determining Amount of Oxygen Delivered to Tissues Each Cycle
| Mixed venous blood entering lung after one cycle ---- PO2 =
40
110
Determining Amount of Oxygen Delivered to Tissues Each Cycle
Oxygenated blood leaving lung after exchange ---
PO2 =
100
111
Determining Amount of Oxygen Delivered to Tissues Each Cycle
| Content Oxygen Oxygenated =
20.85 x 97.5% + 0.3 (dissolved amount) = 20.6 mL
112
Determining Amount of Oxygen Delivered to Tissues Each Cycle
| Content Oxygen Mixed Venous =
20.85 x 75% + 0.12 (b/c dissolved depends on PO2) =
15.7 mL
Therefore, ~5 mL of oxygen is removed from each 100 mL of blood in one cycle
113
Three Forms Carbon Dioxide in Blood
1. Dissolved = 10%
2. Bicarbonate = 60%
3. Carbamino Compounds (~30%)
114
Three Forms Carbon Dioxide in Blood
| Dissolved = 10%
More dissolved than oxygen b/c ↑solubility
115
Three Forms Carbon Dioxide in Blood
| 2. Bicarbonate = 60%
CO2 + H2O --> H2CO3 --> Bicarb + H+
116
Three Forms Carbon Dioxide in Blood
2. Bicarbonate = 60%
CO2 dissolves into tissue and into red blood cell because?
Intracellular CO2 is being used by ↑Carbonic anhydrase in RBC.
117
Three Forms Carbon Dioxide in Blood
2. Bicarbonate = 60%
What happens to the Bicarb + H+ generated in the RBC in tissues?
- Important!!! Hydrogen ion quickly binds to deoxy-Hb; this prevents reforming of carbonic acid, forcing bicarbonate out (“chloride shift”)
- Therefore, the uptake of CO2 from tissue continues because the reaction continues moving to the right
118
Three Forms Carbon Dioxide in Blood
2. Bicarbonate = 60%
In lung the RBC's Hb does what?
O2 binds Hb, leaving the hydrogen to bind bicarbonate and form carbonic acid --> forms CO2 --> exchange!
119
Three Forms Carbon Dioxide in Blood
| 3. Carbamino Compounds (~30%)
- Amino terminal of Hemoglobin binds to CO2
- Hb-NH2 ----> Hb-NHCOOH
- Hb binds CO2 very strongly than HbO2
120
General Features of the Oxygen Hb Curve
| Sigmoidal shape comes form?
Positive cooperativity (↑affinity for additional oxygen)
121
General Features of the Oxygen Hb Curve
| P50 =
Partial pressure at which Hb is 50% saturated
| - Becomes a measure of affinity
122
General Features of the Oxygen Hb Curve
| ↑P50 means that?
Greater pressure required for 50% saturation, so ↓affinity.
123
General Features of the Oxygen Hb Curve
| ↓P50 means that?
Less pressure required for 50% saturation, so ↑affinity
124
General Features of the Oxygen Hb Curve
Loading/Unloading
Region of curve ~40-60 mmHg is ideal for?
Unloading
125
General Features of the Oxygen Hb Curve
Loading/Unloading
Region of curve ~60-100 mmHg is ideal for?
Loading
126
Think: lungs and systemic blood are at 100 mmHg, where affinity is maxed out?
We want this b/c we want Hb to grab oxygen. (Loading)
127
Think: tissues and mixed venous blood (post tissue blood) are at 40 mmHg, where affinity is low because ↓PO2 = ↓Saturation = ↓affinity?
This is good for tissues that need ↑oxygen (unloading)
128
Shifts in the Curve Oxygen Hb Curve
| Right Shift =
Right Shift = ↓Affinity (↑P50) --- ↑unloading of oxygen
129
Shifts in the Curve Oxygen Hb Curve
Right Shift
Causes
1. ↑PCO2 -- need ↑PO2
2. Low pH (↑PCO2) -- from proton + (bicarbonate)
3. ↑Temperature -- think exercise - need more O2 (and get hot)
4. ↑2,3 DPG (glycolysis RBC byproduct) -- occurs in hypoxemia b/c ↓ATP, ↓gly
130
Shifts in the Curve Oxygen Hb Curve
Left Shift
Causes
1. ↓PCO2
2. High pH
3. ↓Temperature
4. ↓2,3 DPG
131
Carbon Dioxide Dissociation Curve
| Two big differences from oxygen curve:
1. Straight line -- cooperativity does not hold true for CO2.
2. Steep line -- small ΔP CO2 = MASSIVE ↑ CO2 content.
132
Carbon Dioxide Dissociation Curve
Artery vs. Vein
Artery has ↑HbO2 and?
Does not bind CO2 well
133
Carbon Dioxide Dissociation Curve
Artery vs. Vein
Vein has ↓HbO2 (↑Hb) and?
Does bind CO2 well
134
Changes in Oxygen vs. Carbon Dioxide
From Right Atrium ---> Left Atrium (aka during gas exchange)
PCO2
Drops from 45 --> 40 b/c it is expired.
135
Changes in Oxygen vs. Carbon Dioxide
From Right Atrium ---> Left Atrium (aka during gas exchange)
PO2
Rises from 40 --> 100 b/c it is inspired
136
Problem? Respiratory quotient CO2 and O2 exchange is 0.8, but the above suggests that a 5 mmHg Δ in CO2 is matched by a 60 mmHg Δ in O2
Answer! B/c ↑steepness in CO2 curve from strong binding with deoxy-Hb, the massive change in Hb CO2 saturation (CO2 content) matches the massive change in Hb O2 saturation content (O2 content)
137
Ventilation/Perfusion Relationships
Review of Pulmonary Blood Flow
1. PBF =
2. PBF =
CO of the right heart = CO of left heart
| ΔP/R = (P_pulmonary-artery - P_left atrium)/Resistance
138
Ventilation/Perfusion Relationships
Review of Pulmonary Blood Flow
Compared to systemic circulation, PBF has?
↓pressure and resistance
139
Ventilation/Perfusion Relationships
Review of Pulmonary Blood Flow
Systemic and PBF have the same?
The flow is same because ↓pressure and resistance is proportionally ↓ than systemic pressure
140
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Hypoxic Vasoconstriction
PAO2
Most important regulator of PBF
141
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Hypoxic Vasoconstriction
↓PAO2 =
Pulmonary vasoconstriction = hypoxic vasoconstriction
142
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Hypoxic Vasoconstriction
Pulmonary vasoconstriction due to ↓PAO2?
At first this is backwards from other tissue beds, where ↓O2 led to vasodilation; BUT, think of this as a protective mechanism, in that ↓O2 areas there is a ↓in blood flow as to not “waste” the blood flow.
143
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Hypoxic Vasoconstriction
Bottom line: hypoxic vasoconstriction keeps?
Pulmonary blood flow away from non-effective alveoli.
144
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Mechanism of Hypoxic Vasoconstriction
Recall that the alveoli and the pulmonary capillaries are?
Intimately associated at alveolar duct level.
145
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Mechanism of Hypoxic Vasoconstriction
B/C O2 is lipid soluble?
It can diffuse across alveolar cell membranes into smooth muscle cells of the arterioles.
146
```
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Mechanism of Hypoxic Vasoconstriction
If O2 drops under 70 from 100, the arteriolar smooth muscle cells?
How?
```
Will sense hypoxia and will constrict
| Hypoxia = depolarization = Ca+ entry = contraction
147
```
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Mechanism of Hypoxic Vasoconstriction
Global Hypoxic Vasconstriction
High Altitude =
```
Because of ↓Barometric Pressure there is ↓PO2 -----> thus, there is global constriction of pulmonary vasculature
148
```
Ventilation/Perfusion Relationships
Regulation of Pulmonary Blood Flow
Mechanism of Hypoxic Vasoconstriction
Global Hypoxic Vasconstriction
Fetal Circulation =
```
Because fetus does not breath, same thing happens, there is global constriction of pulmonary vasculature.
In both these cases, the
vasoconstriction = ↑Resistance = ↓Flow
149
Acid/Base
| Review - Henderson Hasselbach Equation =
pH = pKa + log([Bicarbonate]/[CO2])
150
Acid/Base
Review
Bicarb/carbon-dioxide =
20 when pH = 7.4
151
Acid/Base
Review
Recall simplified formula:
pH α H+ = 24 (CO2)/(HCO3)
152
Acid/Base
Review
If ↓↓HCO3 > ↓CO2 ---->
Metabolic acidosis with compensatory respiratory alkalosis (hyperventilation)
153
Acid/Base
Review
If ↑↑HCO3 > ↑CO2 --->
Metabolic alkalosis with compensatory respiratory acidosis (hypoventilation)
154
Acid/Base
Review
If ↑↑CO2 > ↑HCO3 --->
Respiratory acidosis with compensatory metabolic alkalosis.
155
Acid/Base
Review
If ↓↓CO2 > ↓HCO3 --->
Respiratory alkalosis with compensatory metabolic acidosis.
156
Control of Breathing - Frequency and Tidal Volume
| Five Physiologic Components to Breathing Control
Control of Breathing - Frequency and Tidal Volume
A.Five Physiologic Components to Breathing Control
1.Chemoreceptors
2.Mechanoreceptors in lungs/joints
3.Control centers of the brainstem
4.Respiratory Muscles (run by brainstem)
5.Voluntary commands via cerebral cortex
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Chemoreceptors 2 Types
1. Central Chemoreceptors: sense pH in CSF and communicate directly with inspiratory centers, follow the image:
2. Peripheral Chemoreceptors: Carotid Bodies
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Central Chemoreceptors
Mechanism
(1) BBB is impermeable to H+/Bicarb, but is permeable to CO2
(2) CO2 cross from blood --> brain --> CSF
(3) CO2 + H2O ---> Bicarb + H+ (acid source!)
(4) ↑PCO2 = ↓pH ==== ACIDOSIS
(5) ↓pH is recognized by central chemoreceptors
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Central Chemoreceptors
↓pH is recognized by central chemoreceptors
Acidosis needs to be compensated with alkalosis. For the lungs (compensatory respiratory alkalosis) achieved by ↓CO2 = hyperventilating
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Central Chemoreceptors sense Acidosis
Central chemoreceptors signal --> inspiratory center of medullary respiratory center to ↑breathing rate (hyper)
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Peripheral Chemoreceptors
Mechanism
(a) ↓P_arterial_O2: arterial oxygen!
i) ONLY when PO2 < 60 mmHg
(b) ↑P_arterial_CO2: arterial carbon dioxide!
i) Not as sensitive as PO2-sensing function; recall, CO2 recognition is mainly for central chemoreceptor
(c) ↓pH = ↑breathing (similar to central chemoreceptors)
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Mechanoreceptors in lungs/joints
Lung Stretch Receptors =
Hering-Breuer Reflex
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Mechanoreceptors in lungs/joints
Lung Stretch Receptors
When lung is stretched because of breathing?
There is a response to prolong expiration to prevent hyperventilation.
↑Stretch = ↑Expiration time = ↓Breathing Rate
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Mechanoreceptors in lungs/joints
Muscle/Joint Receptors =
Movement of muscles and joint signals for ↑breathing
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Mechanoreceptors in lungs/joints
Irritant Receptors =
Within epithelial linings, these signal via CN X to constrict bronchiole smooth muscle = ↑breathing rate
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Mechanoreceptors in lungs/joints
J Receptors =
Alveolar walls near capillaries.
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Mechanoreceptors in lungs/joints
J Receptors
When pulmonary capillaries are huge (left-sided heart failure with pulmonary edema)?
These J receptors ↑breathing rate. Produce the signs and symptoms of pulmonary insufficiency from LSHF = SOB.
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem Three
1. Medullary Respiratory Center
2. Apneustic Center
3. Pneumotaxic Center
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Medullary Respiratory Center =
Inspiratory center (dorsal respiratory group) + expiratory center (central respiratory group)
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Medullary Respiratory Center
Inspiratory Center:
Controls rhythm of breathing by setting frequency.
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Medullary Respiratory Center
Inspiratory Center:
Afferent information
Received from CN IX (chemoreceptor) + CN X (chemoreceptor + lung mechanoreceptor)
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Medullary Respiratory Center
Inspiratory Center:
Efferent information
Output from phrenic nerve
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Medullary Respiratory Center
Inspiratory Center: Inhibition
Inspiratory Center can be shortened via inhibition from pneumotaxic center
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Medullary Respiratory Center
Expiratory Center:
Selective control of expiration
| “Selective” b/c expiration is generally a passive process; in some conditions (exercise) neurons here are activated
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Apneustic Center =
Abnormal prolongation of inspiration
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Apneustic Center
Apneustic center neurons excite the inspiratory center=
↑efferent firing to phrenic nerve = ↑diaphragm =
| ↑inspiration
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Control centers of the brainstem
Pneumotaxic Center =
Turns off inspiration via ↓↓AP to phrenic nerve = ↓rate + ↓tidal volume
Normal breathing rhythm exists in absence of the pneumotaxic center
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Respiratory Muscles
Run by brainstem
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Control of Breathing - Frequency and Tidal Volume
Five Physiologic Components to Breathing Control
Voluntary commands via cerebral cortex can?
Temporarily override involuntary brainstem centers
| Examples = hypoventilation + hyperventilation (self-limiting because person will pass out and then breath normally)
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Some Facts for Pharm/Pathology
| Walls of conducting airways have smooth muscle under?
Sympathetic and parasympathetic control
182
Sympathetics (beta-2 receptors):
Dilation/relaxation of airways
183
Parasympathetics (muscarinic cholinergic):
Constrict airways
184
Asthma is treated with?
beta-2 adrenergic agonists, which dilate the conducting airways (epi, isoproterenol, albuterol)
185
Pulmonary Blood Flow =
Cardiac Output of the Right Ventricle via Pulmonary Arteries
186
Pulmonary blood flow changes with position because?
Gravitational effects
187
When standing, pulmonary blood flow is lowest at the?
Apex of the lung; gravity has no effect when laying down
188
Pulmonary blood flow changes with altering?
Resistance of pulmonary arterioles (arterioles!!!); regulated mainly by local oxygen
189
Bronchial circulation:
part of pulmonary blood flow that goes to conducting airways.
***Does not participate in gas exchange.
