Constanzo Chapter 5- Respiratory Physiology Flashcards
(233 cards)
1
Q
Conducting Zone
A
Brings air into and out of the lungs.
2
Q
Respiratory Zone
A
Lined with alveoli, where gas exchange occurs.
3
Q
Components of the Conducting Zone
A
Nose, Nasopharynx, trachea (main), bronchi, bronchioles, terminal bronchioles.
4
Q
Conducting airways smooth muscle Sympathetic innervation
A
Adrenergic neurons activate B2 receptors.
Leads to increases in airway diameter, resulting in relaxation and dilation.
Epinephrine from the adrenal medulla and B2-adrenergic agonists (Isoproterenol).
5
Q
Conducting airways smooth muscle Parasympathetic innervation
A
Cholinergic neurons activate muscarinic receptors.
Leads to decrease in airway diameter contraction and constriction of the airways.
Ex. Muscadine and carbachol.
Can be blocked by muscarinic antagonists (like atropine).
6
Q
Treatment for asthma
A
B2-adrenergic agonists.
Epinephrine
Isoproterenol.
Albuterol.
They dilate the airways.
7
Q
Respiratory Zone structures
A
Respiratory Bronchioles
Alveolar ducts
Alveolar sacs.
8
Q
Respiratory Bronchioles
A
Transitional structures. They have cilia and smooth muscle, but alveoli occasionally bud off their walls.
9
Q
Alveolar ducts
A
Completely lined with alveoli, but they contain no cilia and little smooth muscle.
10
Q
Alveoli
A
Pouchlike evaginations of the walls of the respiratory zone.
300 million alveoli per lung.
200 micrometers in diameter.
Large surface area to facilitate gas exchange.
RImmed with elastic fibers, epithelial cells, type I and type II pneumocytes.
11
Q
Type II Pneumocytes
A
Produce Surfactant.
Have regenerative capacity for type I and II.
12
Q
Alveolar Macrophages
A
Keep the alveoli free of dust and debris.
13
Q
Pulmonary blood flow
A
Cardiac output of right heart.
Delivered by the pulmonary artery from the left ventricle.
14
Q
Gravitational Effects on pulmonary blood flow.
A
When standing:
- Lowest at the apex of the lungs
- Highest at the base.
When lying down:
Irrelevant.
15
Q
Bronchial Circulation
A
Blood supply to the conducting airways, very small fraction of the pulmonary blood flow.
16
Q
Spirometer
A
Measures static volumes of the lung.
Measured by displacing a bell.
17
Q
Tidal Volume
A
500mL (Including air that fills the alveoli AND the airways)
Volume of air inspired of expired during normal, quiet breathing.
18
Q
Inspiratory Reserve Volume
A
3000 mL
Additional volume that can be inspired above the tidal volume.
19
Q
Expiratory Reserve Volume
A
1200 mL
Additional volume that can be expired below the tidal volume.
20
Q
Residual Volume
A
1200mL
Volume of gas remaining after a maximal forced expiration.
21
Q
Inspiratory Capacity
A
IC. 3500 mL (500 +3000)
Tidal volume plus the inspiratory reserve volume.
22
Q
Functional Residual Capacity
A
FRC. 2400 mL (1200 + 1200)
Expiratory Reserve Volume + Residual Volume.
Volume remaining in the lungs after a normal tidal volume is expired.
23
Q
Equilibrium Volume of the lungs
A
Functional Residual Capacity.
24
Q
Vital Capacity
A
VC. 4700 mL (3500 +1200)
Inspiratory capacity + Expiratory reserve volume.
Volume that can be expired after maximal inspiration.
Value increases with:
Body size
Male Gender
Physical Conditioning
Decreases with:
Age
25
Total Lung Capacity
TLC. 5900 mL (4700+1200)
Vital capacity plus the residual volume.
26
Spirometer Limitations
Cannot measure Residual Volume, therefore cannot measure quantities that depend on it either (FRC, TLC).
Other methods must be taken into account to measure FRC, the equilibrium volume.
27
Methods for measuring FRC
Helium Dilution
Body Plethysmograph
28
Helium Dilution
The subject breathes a known amount of helium, added to the spirometer.
Because it is insoluble, it goes into the lungs. The amount in the lungs, measured by the spirometer is used to "back-calculate" the lung volume.
If it is done after a normal tidal volume is expired, the volume is the FRC.
29
Body Plethysmograph
Variant of Boyle's Law:
At constant T, PXV= constant.
If one increases, the other must decrease.
The subject is placed in a box and after expiring a normal tidal volume. The mouthpiece is closed and then he attempts to breathe, so the volume in his lungs increases while the pressure drops. This leads to a increase in box pressure which is measurable.
30
Dead Space
Volume in the airways and lungs that does not participate in gas exchange.
31
Anatomic dead space
Volume of the conducting airways.
150mL.
32
Physiologic Dead Space
Functional dead space.
Total volume of the lungs that does not participate in gas exchange.
Ventilated alveoli that do not participate in gas exchange.
Due to a mismatch of ventilation and perfusion.
33
Ventilation/perfusion defect
Ventilated alveoli are not perfused by pulmonary capillary blood.
They constitute an increase in the physiologic shunt.
Shunt increases-> not fully arteriolized.
34
Volume of physiologic dead space Theory
Based on:
Measurement of partial pressure of CO2 of mixed expired air (PeCO2) and:
1. All of the CO2 in expired air comes from exchange in alveoli.
2. No CO2 in inspired air.
3. The physiologic dead space neither exchanges nor contributes CO2.
If dead space is zero, then PeCO2 will be equal to alveolar PCO2.
35
Difficulties of measuring physiologic dead space
Alveolar air cannot be sampled. One must use PCO2 of Systemic arterial blood and assume it is equal to PCO2 of alveolar air.
36
Volume of Physiological dead space (Formula)
VD= VT x ((PaCO2-PECO2)/PaCO2)
Where VD= Physiological Dead Space
VT= Tidal Volume
PaCO2= PCO2 of arterial blood
PECO2= PCO2 of mixed expired air.
The fraction represents the dilution of alveolar PCO2 by the dead space air.
37
Ventilation Rate
The volume of air moved into and out of the lungs per unit of time.
38
Minute Ventilation
Total rate of air movement into and out of the lungs.
Minute ventilation= VTxBreaths/min.
39
Alveolar ventilation
Corrects for physiological dead space.
VA= (VT-VD) x Breaths/min.
There is an inverse relationship between the alveolar ventilation and alveolar PCO2 (PACO2).
Another way to express this is:
VA=VCO2xK/PACO2.
Where K=863mmHg for BTPS (Body Temperature (310 K), Ambient Pressure (760 mmHg)and gas Saturated with water vapor.
40
Alveolar gas equation
Used to predict the alveolar PO2 based on the alveolar PCO2.
PAO2=PIO2-(PACO2/R)+Correlation Factor.
Where
PIO2= PO2 in inspired air (mmHg)
R= Respiratory exchange ratio or respiratory quotient. (CO2 production/O2 consumption) Normal value is 0.8
41
Forced vital Capacity
FVC. Total volume of air that can be forcibly expired after a maximal inspiration.
42
FEV1
volume of air that can be forcibly expired in the first second.
43
FEV2
Commutative volume of air expired after 2 seconds.
44
FEV3
Commutative volume of air expired after 3 seconds.
45
FEV4
Non-Existant. Air can be expelled in 3 seconds.
46
Normal person FEV1/FVC
0.8, 80% of the vital Capacity can be expired in the first second of forced expiration.
47
FEV1/FVC in obstructive lung disease.
IE. Asthma.
Both FVC and FEV1 are decreased, but FEV1 is decreased MORE.
Indicative of resistance to expiratory flow.
48
FEV1/FVC in restrictive lung disease
IE. Fibrosis.
FVC and FEV1 are decreased but FEV1 is decreased LESS.
The ratio therefore is actually increased from 0.8.
49
Muscles of Inspiration
Diaphragm.
External intercostal muscles.
Accessory muscles.
Vigorous respiration during exercise.
50
Muscles of Expiration
Usually a passive process driven by a reverse gradient.
During exercise or airway increased resistance,
Abdominal muscles.
Internal intercostal muscles.
51
External intercostal muscles
Pull the ribs upward and outward.
52
Diaphragm
Pushes abdominal contents downward and the ribs are lifted upward and outward.
Increase in intrathoracic volume, decrease in intrathoracic pressure.
53
Abdominal muscles
Compress abdominal cavity and push the diaphragm up.
54
Internal intercostal muscles
Pull the ribs downward and inward.
55
Compliance
Distensibility of the system.
How volume changes as a result of a pressure change.
INVERSELY correlated with elastence.
56
Transmural pressure
Pressure across a structure.
Alveolar pressure minus the intrapleural pressure.
If it is positive, it is expanding.
57
Transpulmonary pressure
Difference between the intra-alveolar and intrapleural pressure.
58
Pressure-Volume loop
Sequence of inflation followed by deflation.
The slope of each limb is the compliance of the isolated lung.
59
Expanding Pressure
Negative pressure that expands the lungs along the inspiration limb of the pressure volume loop.
60
As the expanding pressures get higher... effect on compliance?
Compliance decreases.
61
Hysteresis
The slopes for inspiration and expiration are different in the pressure volume loop.
For a given outside pressure the volume of the lung is greater during expiration than inspiration.
62
Measurement of Compliance in Pressure volume loop
In the expiration limb, because the inspiration limb is complicated by the decrease in compliance near maximal expanding pressures.
63
Surface tension
Explanation for hysteresis.
The forces between liquid molecules in the lung are stronger than the forces between liquid and air molecules.
64
Inspiration limb
Low lung volume- molecules are closest together and intermolecular forces are strongest.
The lung surface area is increasing faster than the rate of surfactant addition, thus surfactant density is low and compliance is low. (Flat curve).
As density increases, surface tension decreases and compliance increases, as does the slope of the curve.
65
Surfactant
Phospholipid produced by alveolar type II cells that functions as a detergent to reduce surface tension and increase lung compliance.
66
Expiration limb
Begins at high lung volume.
Lung surface area decreases faster than surfactant removal, thus density of surfactant increases rapidly, leading to an increase in compliance. Thus the initial portion is flat.
It then gets relatively constant.
67
Negative interplural pressure
Created by two opposing elastic forces pulling on the intrapleural space:
1. Lungs tend to collapse.
2. Chest wall tends to spring out.
They create a negative pressure or vacuum.
68
Pneumothorax
Air enters the intrapleural space. Intrapleural pressure suddenly becomes atmospheric pressure (zero) and lungs collapse and chest wall expands.
69
Airway pressure for the lung/chest wall system is zero at which volume?
The Functional Residual Capacity. FRC.
70
Compliance for the lung and chest-wall system?
Lower than the individual compliances.
71
When the volume of the pressure volume curves is FRC?
Airway pressure is zero for the system.
Collapsing force in the lungs is exactly equal to the expanding force on the chest wall.
72
When the volume of the pressure volume curves is less than FRC?
Expanding force on the chest wall is greater than the collapsing force on the lungs.
System expands.
73
When the volume of the pressure volume curves is greater than FRC?
Collapsing force on the lungs is greater than the expanding force of the chest wall.
System collapses.
At really high volumes over the FRC, both systems could lead to collapse. As the chest wall curve crosse the vertical axis as at high volumes.
74
Effect of lung disease on chest wall
None.
75
Effect of increased lung compliance on lung?
EX. Emphysema. Decrease in elastic tissue in the lungs.
The curve gets steeper. Thus at a given volume, the collapsing force is decreased.
Higher FRC.
76
Barrel-shaped chest
Effect of emphysema patients breathing at higher volumes and having a higher than usual FRC.
77
Effect of decreased lung compliance in lung?
EX. Fibrosis. Restrictive disease, associated with stiffening of lung tissues.
Decreased slope of the volume pressure curve.
Lower FRC.
78
Law of Laplace
P=2T/r
Where
P is the Collapsing pressure on the alveolus. (Dynes/cm2)
T is the Surface Tension (dynes/cm)
r is the radius of the alveolous (cm)
Alveoli are more likely to collapse the smaller they are, but need to be as small as possible to maximize surface area for exchange of gases.
79
Most important constituent of surfactant?
Dipalmitoyl phosphatidylcholine (DPPC).
80
DPPC
Amphipatic molecules composing the surfactant that align themselves on the alveolar surface, breaking up the attracting forces between liquid molecules.
They reduce surface tension and collapsing pressure.
81
Neonatal respiratory distress syndrome
Infants born before week 24 will never have surfactant.
Those born between weeks 24 and 35 will have uncertain surfactant status.
Small alveoli will have increased surface tension and increased pressures. They will collapse.
Lung compliance is also decreased and work in inflating the lungs will be increased.
Collapsed alveoli cannot participate in gas exchange, leading to hypothermia.
82
Relationship between airflow, pressure and resistance in lungs
Q=deltaP/R
83
Driving force in airflow
Pressure difference.
At rest, alveolar pressure equals atmospheric pressure (0). But during inspiration, the volume of the lung increases, leading to a decreas in alveolar pressure which causes the gradient.
84
Airway resistance
Poiseuille's law
R=8nl/(pi*r^4)
Where
R= resistance
n=viscosity of inspired air.
l=Lenght of the airway
r=radius of the airway.
The fourth power effect causes a really strong dependence of Resistance on radius.
85
Site of highest airway resistance?
Medium-sized bronchi.
Not the smallest airways because they are arranged in parallel, so their total resistance is actually lower than their individual resistance.
86
Factors in changes in airway resistance
ANS
Lung Volume
Viscosity of inspired air.
87
Effect of lung volume on air resistance.
Surrounding parenchyma tissue exerts radial traction on the airways.
High lung volumes-greater traction-decreased resistance.
88
Compensatory mechanism in asthma
Patients with asthma breathe at higher volumes to partially offset the high airway resistance of their disease.
89
Effect of viscosity of inspired air on airway resistance.
Increased viscosity leads to an increase in air resistance (Poiseuille's law).
Seen in deep-sea diving.
Decreased viscosity such as with Helium, leads to a decreased resistance.
90
Phases in the Breathing Cycle
Rest
Inspiration
Expiration
91
Rest
Alveolar pressure is zero and equals atmospheric pressure.
Intrapleural pressure is negative, -5cm H2O.
The Transmural pressure across the lungs is +5 cmH2O, keepin the lungs open.
Volume is FRC.
92
Inspiration
Diaphragm contracts and the thorax volume increases, leading to a decrease of alveolar pressure, to -1. This causes outside air to travel along the pressure gradient and expand the lung.
Intrapleural pressure becomes more negative (-8 towards the end of inspiration)
Volume at the end of inspiration is FRC + TV.
93
Expiration
Alveolar pressure becomes positive because the elastic forces of the lungs compress the greater volume of air in the alveoli.
Air flows out of the lungs until the volume reaches FRC.
94
Forced Expiration in a normal lung
Airway pressure is +25 and alveolar pressure is +35.
Intrapleural pressure rises to +20.
The important thing is to maintain transmural pressure positive to avoid collapse. (Alveolar pressure-intrapleural pressure, 35-20=+15)
95
Forced expiration with Emphysema
Intrapleural pressure is raised the same as in a normal person (20), however because of the diminished elastic recoil (low elastence), alveolar and airway pressures air lower.
Transmural pressure of the airways is -5, making them collapse. Making resistance to airflow much higher, making expiration difficult.
Emphysema patients tend to expire slowly and with pursed lips.
96
General Gas Law
PV=nRT.
The in the gas phase BTPS is used, but in liquid phase STPD is used.
97
BTPS
Body Temperature (310K or 37C)
Ambient Pressure
Gas Saturated with water vapor.
98
STPD
Standard Temperature (273K or 0C)
Standard pressure (760mmHg)
And Dry Gas.
Gas volume at BTPS can be converted to STPD by multiplying the volume by (273/310)x(PB-47/760)
Where PB is barometric pressure and 47 is the water vapor pressure at 37C)
99
Boyle's Law
P1V1=P2V2, for a given temperature.
100
Dalton's Law
The partial pressure of a gas ina mixture of gases is the pressure that the gas would exert if it occupied the total volume of the mixture.
Pix=PB*F
Where F is the fractional concentration of the gas.
For dry gas.
For humidified gas:
Px=(PB-PH2O)*F
Water vapor pressure is equal to 47mmHg at 37C
101
Percentage of gases in barometric air
O2-21%
N-79%
CO2-0%
102
Henry's Law
Cx=Px*Solubility
Where
Cx is the concentration of dissolved gas (mL/100 mL blood)
Solubility is (mLgas/100mLblood/mmHg)
Cx involves only gas that is free in solution.
103
Ficks Law
Vx=D*A*deltaP/deltax
Where
Vx is the volume of gas transferred per unit time
D= diffusion coefficient of the gas
A= surface area.
deltaP= Partial pressure difference of th gas.
Deltax= Thickness of the membrane.
104
Diffusion Coefficient
Combination of dependency on molecular weight and solubility.
The D of CO2 is 20 times higher than that of O2
105
Lung Diffusing Capacity
DL. Combines the diffusion coefficient, the surface area, and the thickness.
It also takes into account the time required for gas to combine with proteins in pulmonary capillary blood.
Can be measured with CO.
106
DL change in Emphysema Patients
Destruction of alveoli results in a decreased surface area, so DL decreases.
107
DL change in Fibrosis Patients
Diffusion distance (membrane thickness) increases so DL decreases.
108
DL change in pulmonary edema Patients
Diffusion distance (membrane thickness) increases so DL decreases.
109
DL change in anemia Patients
Amount of hemoglobin uní red blood cells is reduced, therefore DL is also reduced.
110
DL change in exercise
DL increases because additional capillaries are perfused, increasing surface area.
111
Total gas concentration in solution
Dissolved gas + bound gas+ chemically modified gas.
Only dissolved gas contributes to partial pressure.
112
PO2 in dry inspired air
160mmHg
Barometric pressure times the fractional concentration of O2
113
PO2 of humidified tracheal air
150mmHg
760-47*.21 gives you that total.
You have to correct and account for the diluton of O2 thanks to the water vapor.
114
PO2 in alveolar air
100mmHg.
It is less than inspired air because it leaves the alveolar air and enters pulmonary capillary blood.
115
PCO2 in alveolar air
40mmHg
It leaves pulmonary capillary blood and enters alveolar air.
116
Blood entering the pulmonary capillaries
Mixed venous blood.
40mmHg PO2
46mmHg CO2
117
Blood leaving the pulmonary capillaries
Systemic arterial blood.
PaO2 is 100mmHg and PaCO2 is 40mmHg
118
Physiologic Shunt
A small fraction of pulmonary blood flow bypasses the alveoli and therefore, not arterialized.
Two sources:
1. Bronchial blood flow
2. Small portion of coronary venous blood that drains directly into the left ventricle rather than being oxygenated.
119
A-a difference
Difference in PO2 between alveolar gas and systemic arterial blood.
A-a gradient= (PIO2-PACO2/R)-PaO2.
Is zero normally, but widened in hypoxemia.
120
Diffusion limited gas exchange
The total amount of gas transported across the alveolar capillary barrier is limited by the diffusion process. The important thing is the pressure gradient.
CO is an example of this.
Transport of O2 during strenuous exercise and emphysema or fibrosis.
121
Pefussion limited gas exchange
The total amount of gas transported across the alveolar/capillary barrier is limited by blood flow. The pressure gradient is not maintained.
N2O is an example of this.
122
Why does CO not equilibrate?
Diffusion of CO into the capillary depends on the magnitude of the partial pressure gradient, which is maintained because CO is bound to hemoglobin.
123
Perfusion-limited O2 transport
Equilibriates at about 1/3 of the capillary lenght. SO the only way to increase diffusion of O2 becomes through blood flow.
124
Diffusion limited O2 transport
FIbrosis, strenuous exercise.
In fibrosis the alveolar wall thickens which decreases DL and thus decreases the rate of diffusion.
Though the TOTAL TRANSFER of O2 is still decreased.
Reflected in a decreased PaO2 in systemic arterial blood and decreased PVbarO2 in mixed venous blood.
125
O2 transport at high altitude.
PAO2 is 50mmHg
Mixed venous PO2 is 25mmHg
This leads to a smaller partial pressure gradient which leads to a longer equilibration.
This is exaggerated in fibrosis, where PO2 equilibrates at 30mmHg.
126
% of O2 in blood represented by dissolved O2?
2%
127
Solubility of O2 in blood
0.003mL/100mL of blood/mmHg
128
% of O2 in blood represented by O2 bound to Hemoglobin?
98%
129
Methemoglobin
Iron component of heme moieties is in ferric state (+3).
Does not bind O2.
130
Methemoglobinemia
Is congenital- deficiency of methemoglobin redactase.
Can also be caused of oxidation by nitrites and sulfonamides.
131
Fetal Hemoglobin
Higher affinity for O2 because of the swap of two B chains for Gamma chains.
132
Hemoglobin S
Abnormal B subunits.
Deoxygenated form forms rods, can result in the occlusion of small blood vessles.
133
O2-Binding Capacity
Maximum amount of O2 that can be bound to hemoglobin per volume of blood.
20.1 mL O2/100mL of blood.
134
Amount of O2 bounded by 1g of Hemoglobin
1.34mL
135
Normal concentration of Hemoglobin in blood
15g/100mL
136
O2 content
Actual amount of O2 per volume of blood.
=(O2-binding capacity*%saturation)+Dissolved O2
137
O2 Delivery to Tissues
Determined by blood flow and O2 content of blood.
O2 delivery= cardiac output*O2 content of blood.
138
50% saturation of Hemoglobin?
At 25mmHg
139
Hemoglobin curve levels off?
From 50 to 100 mmHg
140
Sigmodial Shape
Cause by the positive cooperativity between Heme groups for O2 binding.
141
Attachment of the final O2 to hemoglobin occurs at what pressures?
60 to 100 mmHg
142
P50
Point at PO2 at which hemoglobin is 50% saturated.
Decrease in P50, increase in affinity.
Increase in P50, decrease in affinity.
143
In the lungs, what is PaO2?
100mmHg, 100% saturated.
The hemoglobin curve's flat part extends till 60mmHg, meaning that humans can handle great decreases in atmospheric pressure without compromising O2 binding to hemoglobin.
144
What is PvbarO2 in the tissues?
40mmHg, only 75% saturated.
This leads to a lower affinity for O2.
145
How is the pressure gradient in the tissues maintained?
1) Tissues consume O2
| 2) Low affinity assures that O2 will be unloaded more readily from hemoglobin.
145
Factors that shift Hemoglobin curve to the right?
Increases in PCO2 and decreases in pH
Increases in Temperature
Increases in 2,3-diphosphoglycerate (2,3-DPG)
They bring decreased affinity for O2. Increasing P50.
146
Bohr effect
Effect of PCO2 and pH on the O2-hemoglobin dissociation curve.
147
2,3-diphosphoglycerate
Binds to the B chains of hemoglobin to reduce their affinity for O2.
Increases during hypoxia conditions. (Ie. High altitudes)
148
Factors that shift the hemoglobin curve to the left?
Decreases in PCO2 and increases in pH
Decreases in teperature
Decreases in 2,3-DPG concentration
Hemoglobin F.
149
Why does Hemoglobin F shift the O2 curve to the left?
Because it can't bind 2,3-DPG as well, therefore increasing its affinity to O2.
150
How does CO affect the Hemoglobin curve?
It competes with O2 for binding sites on Hb, therefore reducing O2 content in blood and delivery by 50%.
It also shifts the curve to the left, as the sites that DONT bind CO, have an increased affinity for O2 and a lower P50.
151
Erythropoietin
EPO. Glycoprotein growth factor synthesized in the kidneys that serves as a major stimulus for erythropoiesis. Promotes differentiation of proerythroblasts.
152
EPO synthesis
induced as a result of hypoxia.
1. Hypoxia leads to the production of the alpha subunit of the hypoxia-inducible factor 1alfa.
2. It acts on fibroblasts in the renal cortex and medulla to cause synthesis of mRNA for EPO.
3. mRNA directs EPO synthesis.
4. EPO causes differentiation of proerythroblasts.
5. Further steps in development to form mature erythrocytes.
153
Chronic Renal Failure
the decrease in functioning renal mass results in decreased EPO, and erythrocytes.
This leads to decreased Hb and anemia.
Can be treated with recombinant EPO.
154
Forms CO2 is carried in blood
Dissolved
Carbaminohemoglobin
Bicarbonate (quantitatively most important)
155
Concentration of CO2 in solution
2.8mL CO2/100mL blood
Which comes from 40*0.07 (partial pressure* solubility)
156
What percentage of total CO2 content of blood is dissolved?
5%
157
What percentage of the total CO2 is represented by carbaminohemoglobin ?
3%
158
Haladane effect
O2 decreases Hb affinity for CO2
159
What percentage of the total CO2 is represented by HCO3- ?
90%
160
Carbonic Anhydrase
Catalizes the reaction from CO2 and H2O to H2CO3
161
Who buffers H+ in the blood?
Deoxyhemoglobin, which pairs nicely with the Bohr effect.
162
band three protein
Anion exchange protein that performs the Cl-HCO3- exchange in the red blood cells.
163
How does the pulmonary circulation compare to the systemic circulation?
Much lower pressures and resistances, although blood flow is the same.
They are the same because the pressures and resistances are proportionally lower.
164
Regulation of Pulmonary Blood Flow
Hypoxia Vasoconstiction
Other Vasoactive substances.
165
Hypoxic vasoconstriction
Decreases in PAO2 produce pulmonary vasoconstriction.
This helps restrict airflow to sites were it would otherwise be wasted.
It can serve as a protective mechanism in lung disease.
166
Mechanism of vasoconstriction
Direct action of alveolar PO2 on the vascular smooth muscle of the arterioles.
Normally, at 100mmHg, O2 diffuses to the arterioles smooth muscle and keeps them relaxed.
At lower than 70mmHg, the muscles sense this hypoxia en vasoconstrict.
167
Effect of NO on hypoxic vasoconstriction ?
It reduces or offsets hypoxic vasoconstriction.
168
Global effect of vasoconstriction?
Increase in pulmonary vascular resistance, which leads to an increase in pulmonary arterial pressure which then would lead to hypertrophy of the right ventricle, as it pumps against a higher afterload.
Can happen in fetuses as well. Leading to a decrease in pulmonary blood flow to 15% of the cardiac output.
169
Vasoactive substances that alter pulmonary vascular resistance?
Thromboxane A2
Prostacyclin (Prostaglandin I2)
Leukotrienes.
170
Thromboxane A2
Product of arachidonic acid metabolism.
Produced in response to lung injury.
Powerful vasoconstrictor in arterioles and veins.
171
Prostacyclin
Product of arachidonic acid metabolism.
Potent vasodilator.
Produced by lung endothelial cells.
172
Leukotrienes
Product of arachidonic acid metabolism.
Cause airway constriction.
173
zone 1
Because of gravity, Pa may be lower than PA.
If it is lower, then pulmonary capillaries are compressed and closed, reducing regional blood flow.
Normally, Pa is just high enough to avoid this.
Durrinng a hemorrhage (Pa decrease) or Positive pressure breathing (PA increase) the capillaries close and zone 1 becomes part of the physiological deadspace.
174
Zone 2
Pa is higher than in zone 1 and PA.
PA is higher than Pv.
Blood flow is driven by a difference between Pa and PA.
175
ZOne 3
Pa and Pv are higher than PA.
Blood flow is driven by the difference between Pa and Pv.
176
Shunt
Portion of cardiac output that is diverted or rerouted.
177
Types of shunts
Physiologic shunt
Right-to-left shunts
Left-to-right shunts
178
Physiologic shunt
2% of the Cardiac Output bypasses the alveoli.
Explained by:
Bronchial blood flow
Small amount of coronary blood that drains into left ventricle through the Thebesian veins and does not perfuse.
PaO2 will alwways be slightly less than PAO2.
179
Right-to-left shunts
50% of the Cardiac Output can be rerouted if there s a problem with the wall dividing the right ventricle from the left ventricle.
hypoxemia always occurs because C. Output is not delivered to the lungs.
It CANNOT be corrected by breathing high O2 gas.
180
Shunt fraction equation
Blood flow through a right-to-left shunt
Qs/QT=(O2content in normal blood- O2 content in arterial blood)/(O2 content in normal blood- O2 content in mixed venous blood)
Qs= blood flow through the shunt
QT=Cardiac Output
"Normal" blood= nonshunted blood.
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Left-to-right shunts
Do not cause hypoxemia.
Causes:
Patent ductus arteriosus
Traumatic injury.
PO2 in the blood on the right side will be elevated, because oxygenated blood is deposited directly into the right atrium.
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Normal value for V/Q
0.8
If breathing frequency, tidal volume and cardiac output are all normal.
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How V/Q ratio is regionalized
Zone 1> Zone 2> Zone 3.
This produces differences in PaO2 and PaCO2.
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V/Q mismatch
Leads to abnormal gas exchange.
Can be caused by ventilation of lung regions that are not perfused. Or perfusion of regions that are not ventilated.
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Types of V/Q defects
Dead Space
High V/Q
Low V/Q
Shunt
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Dead Space
V/Q= infinite
Ventilation of lung regions that are not perfused.
In Pulmonary embolisms, blood flow to a portion of the lung is occluded
Alveolar gas has same composition as humidified air: PAO2 is 150mmHg and PACO2 is 0.
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High V/Q
Have some blood flow.
High PO2 and low PCO2.
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Low V/Q
Some ventilation. Low PO2 and high PCO2
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Shunt (V/Q=0)
Perfusion of regions that are not ventilated.
No gas exchange.
Airway obstruction or right-to-left cardiac shunts.
Same composition as mixed venous blood in pulmonary capillary blood:
PaO2 is 40mmHg
PaCO2 is 46 mmHg
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Components in breathing control
Chemoreceptors for O2 and CO2
Mechanoreceptors in the lungs and joints
Control centers for breathing in the brain stem
Respiratory muscles, activity directed by the brain stem centers.
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Control of frequency of normal, involuntary breathing
Brain stem centers:
Medullary respiratory center
Apneustic center
Pneumotaxic center
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Medullary Respiratory Center
Located in the reticular formation and is composed of two groups of neurons that are distinguished by their anatomic location: the inspiratory center and expiratory center.
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Inspiratory center
Located in the dorsal respiratory group (DRG) of neurons and controls basic rhythm of breathing by setting frequency of inspiration.
Receives fromCN IX and X, and mechanoreceptors in the lung.
Sends motor output to the diaphragm via the phrenic nerve.
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Expiratory Center
Ventral respiratory neurons.
Inactive during quiet breathing because expiration is a passive process.
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Apneustic Center
In the lower pons.
Produces abnormal breathing with prolonged inspiratory gasps.
Excitement of the inspiratory center, prolonging action potentials in the Phrenic Nerve.
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Pneumotaxic Center
Located in the upper pons.
Turns off inspiration, limiting burst of action potentials in the phrenic nerve.
Limits size of tidal volume and regulates respiratory rate.
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Cerebral Cortex
Commands can temporarily override brain stem centers.
A person can voluntarily hyperventilate or hypoventilate.
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Hyperventilation
Decrease in PaCO2 which causes arterial pH to rise.
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Hypoventilation
Decreases in PaO2, increases in PaCO2.
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Most important sensory information arriving at brain stem?
PaO2, PaCO2, and arterial pH.
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Brain stem chemoreceptors are extremely sensitive to what?
Changes in cerebrospinal fluid pH.
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Medullary chemoreceptors mechanism
1. HCO3- in the blood cannot pass through the blood-brain barrier. It can turn back into water and CO2, which does enter.
2. CO2 also pases through the brain-CSF barrier.
3. CO2 is converted to H+ and HCO3-. Increases in arterial PCO2 lead to decreases in CSF pH.
4. Central chemoreceptors are in close proximity to CSF and detect the decrease in pH,
5. signals the inspiratory center to increase breathing rate.
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Location of the peripheral chemoreceptors?
Carotid bodies in the bifurcation of the common carotid and below the aortic arch.
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Chances that produce an increase in breathing rate by the peripheral chemoreceptors?
Decreases in arterial PO2
Increases in arterial PCO2
Decreases in arterial pH
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Decreases in arterial PO2 in Peripheral chemoreceptors
Relatively insensitive to changes in PO2.
Decreases to less than 60mmHg, increases breathing rate in a steep and linear fashion.
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Increases in arterial PCO2 in peripheral chemoreceptors
Less important than PO2, and less important than detection of CO2 by the central chemoreceptors.
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Decreases in arterial pH by peripheral chemoreceptors.
Cause an increase in ventilation.
Mediated only by chemoreceptors in the carotid bodies.
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Other receptors involved in breathing control besides chemoreceptors?
Lung stretch receptors
Joint and muscle receptors
Irritant receptors
J receptors
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Lung and stretch receptors
Present in the smooth muscle in the airways. Stimulated by distention.
Produce a reflex decrease in breathing rate, the Hering-Breuer reflex.
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Hering-Breuer reflex
Decreases breathing rate by prolonging expiratory time.
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Joint and muscle receptors
Detect movement of limbs and instruct the inspiratory breathing center to increase breathing rate.
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Irritant receptors
For noxious chemicals and particles, located in epithelial cells lining the airways.
Info travels to the medulla via CNX and causes reflex constriction of bronchial smooth muscle and increase in breathing rate.
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J receptors.
Juxtacapillary.
Near the capillaries in the alveolar walls.
Engorden of capillaries may increase interstitial fluid volume and activate them, producing an increase in breathing rate.
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Arterial PO2 and PCO2 during exercise
Do NOT change.
Increased ventilation and increased efficiency of gas exchange ensure this.
Oscillations in their values could be what triggers immeadiate adjustments in ventilation by the chemoreceptors.
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Venous PCO2 in exercise.
MUST increase because of the contribution of skeletal muscle.
The ventilation rate must increase sufficiently to rid the body of this.
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Muscle and Joint receptors in exercise
Send information to the medullary inspiratory center and participate in the coordinated response to exercise.
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Cardiac Output and Pulmonary blood flow during exercise
They increase.
A decrease in pulmonary resistance associated with the perfusion of more capillary beds causes blood flow to be even more evenly distributed.
V/Q becomes even, producing a decrease in physiologic dead space.
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O2-Hemoglobin Dissociation Curve during exercise
Shifts to the right.
Because of decreased pH, increased PCO2, increased temperature.
Increase in P50, decreased affinity for O2 facilitating unloading in skeletal muscle.
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Responses to high altitudes
Hyperventilation
Polycythemia
2,3-DPG increase
Shift of Hemoglobin curve to the right.
Pulmonary vasoconstriction
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Hyperventilation as a response to altitude.
A drop below 60mmHg PO2 will trigger hyperventilation by the peripheral chemoreceptors.
This causes CO2 to be expired and PCO2 to decrease, resulting in respiratory alkalosis.
Can be treated with carbonic anhydrase inhibitors like acetazolamide.
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Polycythemia as a result of high altitude
Hypoxia->EPO->red blood cells-> Hemoglobin-> O2 content
Also increases viscocity and therefore increases resistance.
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Pulmonary vasoconstriction as a consecuence of high altitudes.
High altitude->low PO2-> hypoxic vasoconstriction.
Increased resistance->increased blood pressure-> increased afterload-> right ventricular hypertrophy.
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Hypoxemia
Decrease in arterial PO2
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Hypoxia
Decrease in O2 delivery or utilization by the tissues
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Causes of hypoxemia
High altitude
Hypoventilation
Diffusion defects
V/Q defects
Right-to-left shunts
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High altitude, in regards to hypoxemia
PB is decreased->decreased PIO2 and PAO2.
Equilibration of O2 across the barrier is normal.
Systemic arterial blood achieves the same PO2 as alveolar air.
Treating with suplemental O2 raises PaO2 by PAO2.
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Hypoventilation in association with hypoxemia
Decrease in PAO2.
Equilibration is normal and PaO2 has same PO2 as PAO2.
Suplemental O2 raises arterial PO2 by raising alveolar PO2.
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Diffusion defects in hypoxemia
Fibrosis, edema.
Increase diffusion distance or decrease surface area.
Eq of O2 is impaired.
PaO2 is less than PAO2.
A-a is widened.
Suplemental O2 raises alveolar PO2 and the driving force.
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V/Q defects in hypoxemia
Always cause hypoxemia and A-a increase.
High V/Q regions have the lowest blood flow, lowest contribution.
Low V/Q regions have the highest blood flow, highest contribution.
Suplemental O2 raises the PO2 of low V/Q regions.
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Right-to-left shunts in the context of hypoxemia
Blood leaving the lungs has less PO2 than normal
Suplemental O2 has little effect, only raises the PO2 of normal, non-shunted blood.
Depends on the size of the shunt. As the shunt grows, the effect is less.
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Hypoxia, causes
Decreased cardiac output and decreased O2 content of blood.
Hypoxemia causes hypoxia because decreased PaO2 decreases percent saturation of Hemglobin
Anemia
CO poisoning
Cyanide poisoning.
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Cyanide poisoning
Interferes with O2 utilization of tissue... does not involve decreased blood flow or decreased O2 content of blood.
