Longmuir Flashcards
1
Q
What are the 6 primary symbols?
A
P = pressure (units: mmHg (most common), cmH2O (which is a smaller pressure unit))
o 760 mmHg = 1 standard atmosphere
V = volume (units: L, mL)
T = temperature (units: *C, K)
o 0C = 273 K
A dot above adds time dimension (in these notes “X*”)
V* = flow or volume of gas/unit time (units: L/sec, mL/min)
F = fractional concentration of a gas in a gas mixture (no units, ranges 0-1)
o Refers to DRY GAS ONLY (no water vapor, it must be first subtracted out)
2
Q
What is P?
A
pressure (units: mmHg (most common), cmH2O (which is a smaller pressure unit))
o 760 mmHg = 1 standard atmosphere
3
Q
What units volume?
A
L, mL
4
Q
What units for temperature?
A
C, K
5
Q
What is Vdot measured in?
A
L/sec mL/min
6
Q
What is F? Refers to what type of gas?
A
fractional concentration of a gas in a gas mixture (no units, ranges 0-1)
Refers to DRY GAS ONLY (no water vapor, it must be first subtracted out)
7
Q
What are the 4 secondary symbols?
A
I = inspired gas that has been saturated with water vapor & warmed to 37*C
o Aka “tracheal air”
o Contains O2, N2 & H2O vapor
A = alveolar gas that has been saturated with water, warmed to 37*C & contains CO2
o Contains O2, N2, H2O vapor & CO2
B = barometric or barometric pressure
E = exhaled gas (usually contains CO2)
8
Q
Primary symbols denote?
A
a Physical quantity
9
Q
Secondary symbols denote?
A
Location
10
Q
Tertiary symbols denote?
A
a particular type of gas such as O2, N2, H2O, CO2, Ne, CO, etc.
11
Q
P_IO2 means?
A
Partial pressure of O2 in the airways (inspired, saturated, and warmed to 37)
12
Q
What is the fractional concentration of O2 and N2 in the atmosphere?
A
FO2=0.21
FN2=0.79
13
Q
What is I? Properties? What does it contain?
A
inspired gas that has been saturated with water vapor & warmed to 37*C
o Aka “tracheal air”
o Contains O2, N2 & H2O vapor
14
Q
What is A? Properties? What does it contain?
A
alveolar gas that has been saturated with water, warmed to 37*C & contains CO2
o Contains O2, N2, H2O vapor & CO2
15
Q
What is B?
A
Barometric pressure
16
Q
What is E?
A
Exhaled gas (usually contains CO2)
17
Q
What is FCO2?
A
0.0004 (usually ignored)
18
Q
What is Pb?
A
760 mmHg
19
Q
Descrbie Dalton’s law
A
Total Pressure = Sum of Partial Pressures = Barometric (usually)
20
Q
Describe Dalton’s Law for Pressure. For Volume?
A
Pz=Ptot x Fz
Vz=Vtot x Fz
21
Q
Describe the process of saturating gas with water vapor in the airways
A
As air enters the airways, it becomes saturated with H2O vapor that exerts its own partial pressure
(vapor pressure) that’s dependent on the temperature of the air & independent of the total
barometric pressures; thus, the total pressure remains the same (760 mmHg)
22
Q
At body temperature, what is the saturating vapor pressure of water?
A
P_IH2O 47 mmHg (at 37 C)
23
Q
Where does gas exchange occur?
A
The alveoli
24
Q
What is the respiratory exchange ratio?
A
R=CO2 production / O2 Consumption
25
Describe R for different fuels burned
R=1 for glucose, R<1 when fat is burned too
26
What is P_ACO2?
The partial pressure of CO2 in the aveoli
| Very tightly regulated to 40 mmHg
27
Describe ideal gases in the human lung? Exceptions?
At room temperature & 1 atmospheric pressure, most gases that we’re concerned about behave as
ideal gases; we can use the ideal gas law & it’s derivatives to understand the human lung
Note: water doesn’t behave like an ideal gas; as you condense it, the water vapor pressure
remains the same because some is condensed
28
What is BTPS? What is reported in BTPS?
body temperature & pressure, saturated
(all lung volumes are reported as BTPS)
P = barometric, T = 37*C, saturated with H2O
29
What is ATPS?
The volume of gas at ambient temperature and pressure, and which is saturated with water vapor.
30
What is STPD?
The volume of a gas at standard temperature and pressure, dry.
T = 0 °C; P = 760 mm Hg; PH2O = 0 mm Hg
31
What is Tidal Volume?
the volume of gas inspired or exhaled
| during normal, quiet breathing
32
What is Vital capacity?
the maximal volume that can be exhaled after maximal inspiration
o By far the most clinically important
33
What is functional residual capacity?
the volume of gas in the lungs at the resting expiratory level (when no muscles are engaged)
34
What is residual volume?
Volume of gas in the lungs at the end of maximal expiration
35
What is total lung capacity?
The volume of gas in the lungs at the end of maximal inspiration
36
What can be measured using spirometry?
Tidal Volume
| Vital Capacity
37
What needs to be measured using other techniques? What can be derived from that?
FRC (like nitrogen washout)
| Then can calculate RV and TLC
38
Describe the nitrogen washout test
Test is started when the lungs are at FRC (resting expiratory level, just ask patient to relax)
Have the patient breath in O2 while hooked up to a machine; O2 will flush out the N2 into the
collection bag such that only O2 & CO2 remain in the lungs
The volume of gas in the bag & fractional concentration of N2 is measured to determine the Vol of N2 at FRC & then FRC is calculated
Since Vol N2 = FRC x 0.8, FRC = Vol of N2 @ FRC/0.8
39
How do we calculate RV, TLC, and FRC from vital capacity? (Approximately)
```
RV = 0.25 VC
TLC = 1.25 VC
FRC = 0.5 TLC
```
40
What is forced vital capacity?
The volume of air exhaled during forced expiration
41
What is FVC - 0.5?
The volume of air exhaled during forced expiration in the first 0.5 seconds
42
What is FVC - 1.0?
The volume of air exhaled during forced expiration in the first 1 seconds
43
What is Forced Expiratory Flow (FEF_25-75)?
The average rate of gas flow measured between 25% and 75% of forced vital capacity
44
Describe lung function with height and age?
Lung function is positively correlated with height & negatively correlated with age
(downhill after age 20)
45
Describe how to use a nomogram for normal values of forced expiration
Use a ruler to draw a line across the age & height of a person to read off the various
predicted lung functions
```
There is a wide range of normal values (to include 95% of the population, one needs to
include 2 standard deviations; thus a person would have to lose 1/3 of his/her lung
function before being considered abnormal)
```
46
Describe normal FVC, FEV1.0/FVC, and TLC
o FVC 70% of predicted value (using nomogram)
o FEV1.0/FVC 75% (means that a person should be able to expel most of their air in less than 1 sec)
o TLC 70% of the predicted value (obtained by multiplying predicted FVC by 1.25)
47
What is obstructive ventilatory defect?
decreased rate of flow out of the lungs due to narrowed/blocked airways
48
What is the pattern for obstructive ventilatory defect?
A. FVC reduced < 70% of predicted value
(some exceptions in emphysema)
B. FEV1.0 / FVC < 75% (always)
C. TLC normal or above normal
D. FRC normal or above normal
49
What causes obstructive ventilatory defects?
asthma, chronic bronchitis, emphysema & COPD
50
What is restrictive ventilatory defect?
decrease in total volume of air the lungs can hold, often due to decreased elasticity or a problem related to the expansion of the chest wall during inhalation
51
What is the pattern for restrictive ventilatory defect?
A. FVC reduced < 70% of predicted value
B. FEV1.0 / FVC >= 75%
C. TLC reduced
D. FRC reduced
52
What are the causes of restrictive ventilatory defect?
Causes: fibrosis, chest wall deformities, pneumothorax, pleural fluid & neuromuscular impairment (notice that usually nothing’s wrong with the lungs, it’s the surrounding that’s abnormal)
53
For flow-volume loops, what are the axes?
X axis = volume
| Y axis = flow rate
54
Flow volume loop for an asthmatic would show?
no problem breathing
in but exhaling is troublesome
(look at V*50)
55
What is anatomical dead space? How is it estimated?
Anatomical dead space = the volume of the conducting airways (i.e. trachea)
o Almost never changes in pulmonary disease
o Rule of thumb: body weight (lb) approximately equals to anatomical dead space volume (ml)
56
What is apparatus dead space?
the dead space created by adding a breathing device & thus tidal volume needs to be adjusted accordingly
57
What is physiological dead space?
the volume of the conducting airways + non-functioning alveolar regions (ventilated with air but not perfused with blood)
58
What is physiological dead space usually measured as?
VD/VT (ratio of dead space to tidal volume)
59
Physiological dead space effect on partial pressure of CO2?
Doesn’t evolve CO2; hence, the partial pressure of CO2 in the exhaled gases is lower than the partial pressure of CO2 in the alveoli
60
What is normal physiological dead space? Diseased?
VD/VT = 0.25 is normal; VD/VT = 0.5 is diseased; VD/VT = 0.75 is very diseased but survivable
61
What is the Bohr equation?
VD/VT = (PACO2 – PECO2)/PACO2
62
What does the Bohr equation state?
States that physiological dead space is tidal volume multiplied by a fraction that represents
the dilution of alveolar PCO2 by dead-space air, which doesn’t participate in gas exchange &
therefore doesn’t contribute CO3 to expired air
63
How do we use Bohr equation to get physiological dead space?
Exhaled gas is used to obtain PECO2
Arterial blood sample (PaCO2) is used to obtain PACO2
64
What is f?
Respiratory frequency (breaths per minute)
65
What is the ventilatory rate?
f x Tidal volume
66
What is dead space volume?
Tidal Volume X (Dead space volume/Tidal Volume)
67
What is alveolar ventilation?
```
f x (V_T - V_D)
How much air gets to alveolar region
```
68
In lung mechanics, what are pressures measured to? What is assumed if the glottis is open?
all pressures are relative to atmospheric (thus, Patm = 0 cm H2O)
o If the glottis is open, no air flow is occurring & no mechanical device is attached to the mouth, the alveolar pressure is always equal to the atmospheric pressure
69
How is pressure difference calculated?
measured as inside minus outside ΔP = pressure(in) – pressure(out)
70
What is transpulmonary pressure?
Transpulmonary pressure (pressure difference across the lung wall) = PA – Ppl
71
What is the pressure difference across the chest wall?
Pressure difference across the chest wall = Ppl – Patm
72
Describe elastic recoil
If you have to apply a + pressure to inflate the lung, there must be a force trying to collapse the lung (elastic recoil)
o If you apply negative (subatmospheric) pressure around the lungs, the lungs will inflate
73
What does elastic recoil depend on? What is it independent of?
Elastic recoil depends on lung volume but is independent of the method by which the lungs are inflated
74
Describe the lungs within the thoracic cage when there is no muscular effort and the glottis is open
When there’s no muscular effort & the glottis is open, the lungs are at FRC & PA = Patm = 0 cm H2O
75
Describe elastic recoil of the lungs
Elastic recoil of the lungs = PA – Ppl
this is positive, meaning the lungs will collapse
NB. Elastic recoil pressure is drawn inward on lungs by convention
76
Describe elastic recoil of the chest wall
Elastic recoil of the chest wall = Ppl – Patm
this is negative, meaning the chest wall will expand
NB. Elastic recoil pressure is drawn inward on lungs by convention
77
Why is the respiratory system stable at FRC (no muscles, and glottis open)?
The balance of forces (lung tendency to collapse & chest wall tendency to expand outward) makes the respiratory system stable at FRC
78
What happens if air enters the pleural space?
Respiratory system is stable as long as the system is sealed; if air enters the pleural space, the lungs will collapse
o Pneumothorax = air in lungs (i.e. GSW); hemothorax = blood in lung (i.e. stab wound)
79
How is subatmospheric pleural space maintained?
Physiologically maintain the subatmospheric pleural space by (1) gas reabsorption into the venous circulation & (2) fluid reabsorption by osmotic forces (pleural fluid has less protein than plasma)
80
What is the function of pleural fluid?
Pleural fluid simultaneously acts as a lubricant to allow the lung & chest wall to slide over one another and a glue to allow the chest wall & lung to adhere to one another
81
What is lung compliance? (in words)
LUNG COMPLIANCE = Indicates how easy (higher values) or hard (lower values) it is to inflate the lung
82
Compliance is defined by? How is it measured?
Compliance = elastic recoil as a function of lung volume = ΔV / ΔP
Measured (infrequently) by measuring volume change using a spirometer & pressure difference across the lung via a swallowed esophageal balloon
83
Describe compliance in stiff lungs? Emphysema? Fibrosis?
Stiff lungs = low compliance or high elastic recoil
Emphysema = less elastic recoil & more compliant
Fibrosis = more elastic recoil & less compliant
84
Describe surface tension using water
1 water molecule can make up to 4 H-bonds with surrounding water molecules in a 3D arrangement
o If you place a H2O molecule on a surface, at least 1 H-bond is broken & this is thermodynamically insulting
o H2O will respond by trying to minimize surface area to maximize H-bonds; this behavior is surface tension
85
How do we calculate elastic recoil pressure as a function of surface tension?
Elastic recoil pressure due to surface tension forces: P = 2γ/r
[γ = surface tension & r = alveolar radius]
86
Describe the balancing of surface tension
When the pressure-volume work trying to inflate the lung is balanced by the surface tension-area
work trying to deflate the lung, lung stability results
87
Describe the balance of surface tension at FRC
At FRC, the following forces exist & are balanced (no muscular effort is required):
1. Air pressure difference between alveoli & pleural space working to inflate the lung
2. Combination of surface tension forces & tissue elastic forces to collapse the lung
88
Are alveoli lined with water?
Alveoli aren’t lined with water (if they are, they would collapse)
89
What accounts for the majority of lung elastic recoil?
Alveolar surface tension accounts for most of the lung elastic recoil
90
Describe what lines the alveoli. Composition? Relation to premature infants?
Alveoli are lined with a secreted material called pulmonary surfactant that’s mostly phosphatidylcholine
(FA chains don’t form H-bonds thus strong surface tension forces don’t exist)
Premature infants discover this because they don’t make surfactant until the last month
91
What is alveolar surface tension usually?
<10 dynes/cm
92
Describe surfactant surface tension as a function of lung volume
Surfactant surface tension has to change with lung volume (if not, the smaller one would collapse & empty into the large one); this quality results from compression/expansion of FA
Surface tension decreases with decreasing surface area & lung volume; surface tension increases with increasing surface area & lung volume)
93
Fractional concentration refers to what type of gas
DRY GAS
| MUST always subtract PH20 of 47 mmHg at body temp
94
Describe the 4 steps to generating an airflow in the breathing cycle?
Generating an Airflow
1. The lung itself is incapable of breathing
2. Breathing is accomplished by (1) muscular effort to contract the diaphragm and (2) muscular
effort to expand the rib cage outward (inspiration) or force the rib cage inward (forced expiration)
3. There are no tissue elements connecting the diaphragm and rib cage to the lung
4. The lung is mechanically coupled to the diaphragm/rib cage by pleural fluid hydraulically
95
The lung is connected to the diaphragm/rib cage how?
The lung is mechanically coupled to the diaphragm/rib cage by pleural fluid hydraulically
96
Describe the 4 steps to inspiration
1. Contract diaphragm to expand the size of the thoracic cavity
2. Since lung’s hydraulically-coupled to the diaphragm/chest wall by pleural fluid, lung expands also
3. Now the same amount of air in the lungs is in a larger volume meaning the alveolar pressures
become sub-atmospheric
4. Air flows in until alveolar pressure = Patm (air flows in response to pressure gradient)
97
How do we calculate the direction of airflow?
ERlung = PA – Ppl always holds & can be used to determine airflow direction; solve for PA & if
PA = 0 cm H2O then no flow; PA > 0 cm H2O then air flows out; PA < 0 cm H2O then air flows in
98
How do we classify airway splits?
Airway Classification: 1 splits into 2 & so they are generations: at generation x, we have 2^x airways
99
What is cross-sectional area in lung context? how calculated?
CROSS SECTIONAL AREA: CSA = πr2 While the
CSA of an individual bronchiole is much smaller than the trachea, there are many more such that the CSA of the trachea is the least & so it is the bottleneck!
100
What is the bottleneck of airway?
CSA is smallest in trachea
| Bronchioles have small CSA but there are many of them to increase total effective CSA
101
How is flow velocity calculated?
Velocity = rate of airflow/CSA
| the linear velocity of air is faster in the trachea than in a bronchiole
102
Describe the classification difference between central and peripheral airways
By convention, airways > 2 mm are “central airways” and airways < 2 mm are “peripheral airways”
103
Describe the formulaic relationship of rate of airflow to driving pressure and resistance. Units?
Rate of airflow = driving pressure/resistance reworking of Ohms law: F = P/R
Units of flow = L/sec, units of pressure = cm H2O & units of resistance are cmH2O/(L/sec)
Airway resistance is rarely measured
104
Describe laminar flow. Resistance is proportional to?
LAMINAR FLOW silent; occurs in peripheral airways (because of amount of cross sectional area)
Resistance is proportional to 1/r^4
105
Laminar flow resistance is proportional to?
1/r^4 (pressure is 1:1)
106
Describe turbulent flow. Resistance is proportional to? Pressure?
TURBULENT FLOW makes noise; occurs in central airways, particularly during forced expiration
R 1/ r5 AND increases proportionally with airflow (i.e. if flow doubles, driving pressure must
increase by a factor of 4 [i.e. diaphragm & accessory muscles contract more forcefully])
107
Describe the relationship of pressure and resistance to turbulent flow
resistance is proportilow onal to 1/r^5
| flow proportional to P^2 (e.g. to double airflow, pressure must be quadrupled)
108
What are the ground rules for dynamic compression
Ground rules: (1) Occurs only during forced expiration (2) occurs only when pleural pressures are positive
109
During forced expiration, pleural pressures are ....than Patm
Greater than
110
Describe the pressures during forced expiration
During a forced expiration, the alveolar pressure is positive & counterbalances the pleural pressure & ERlung that are working to
compress/squeeze on the alveolus
ERlung = PA – Ppl; thus, PA = ERlung + Ppl
Air will flow out down the pressure gradient & as it flows the driving pressure will be dissipated & the pressure will drop
111
What is the equal pressure point?
Equal pressure point = point where the air pressure in the airways equals the pleural pressure
112
Describe the areas between equal pressure point and the mouth
Between the equal pressure point & the mouth, pleural pressure is greater than the pressure in the airway & airway compression occurs Dynamic compression primarily occurs in central airways
113
Describe increasing pleural pressure and flow rate response
Above about +10 cm H2O pleural pressure (a mild expiratory effort), further increases in expiratory effort
(as indicated by increase in pleural pressure) produce NO increase in flow rate
114
What is the purpose of diffusion?
The purpose of diffusion is to make the partial pressure of oxygen in the capillary equal to the partial pressure of oxygen in the alveolar gas [mixed venous blood has a textbook value of PO2 = 40 mmHg)
115
Mixed venous blood has a textbook value of PO2 of?
~40 mmHg
116
Describe the states of oxygen from the air to blood
The oxygen must undergo a phase change from a gas in air to a gas dissolved in a liquid
117
How do we determine the partial pressure of oxygen?
Partial pressure of oxygen in air is determined by Dalton’s law: PO2 = FO2 x (Ptotal – PH2O)
118
Describe the relationship between partial pressure of oxygen in air and in liquid
Partial pressure of oxygen in liquid = the partial pressure of oxygen in air when the air & the liquid are in equilibrium
119
What does partial pressure of oxygen in blood include?
Partial pressure of oxygen in a blood doesn’t include O2 bound to Hb, just dissolved O2
120
Describe what determines diffusion (5 things)
Area: increasing area increases diffusion
Diffusion properties of the gas: depends on MW of the gas
Thickness: longer path for diffusion makes diffusion lower (increased with pulmonary fibrosis)
Capacity of blood for the gas: depends on amount of Hb (decreased with anemia (lungs normal))
Partial pressure of gas in the alveoli: diffusion process is slower at high altitudes
121
What effect does area have on diffusion?
Increased by larger person, at TLC vs. RV or during exercise
Decreased by lung resection & emphysema
122
Describe properties of gas on diffusion
Diffusion properties of the gas: depends on MW of the gas
123
Describe thickness effect on diffusion. Disease state?
Thickness: longer path for diffusion makes diffusion lower (increased with pulmonary fibrosis)
124
Describe the capacity of blood for gas?
depends on amount of Hb (decreased with anemia (lungs normal))
125
Describe the partial pressure of gas effect on diffusion.
diffusion process is slower at high altitudes
126
Describe the generalized diffusion capacity of the lung equation
Vgas = DL x (PA – PC)
127
What is D_L?
Diffusing Capacity of the Lung (DL) is these terms lumped (A, diffusion properties of gas, thickness, capacity of blood for the gas, partial pressure of gas in the alveoli)
128
Describe CO diffusion equation
CO bings Hb tightly so that the partial pressure of CO in the capillary is essentially 0… VCO = DLCO x PACO
129
Describe the steady state technique for measuring diffusion capacity
Patient breaths a gas mixture with very dilute CO
Consumption of CO is measured over several minutes (what went in – what comes out)
Average PACO is estimated by mathematical approximations
D_LCO = V*CO /PACO
130
What are the components of D_L?
1/DL = 1/DM + 1/(ΘVC)
131
What is D_M? What reduces it?
DM = membrane diffusing capacity (gas has to cross the membrane)
Reduced in lung resection & emphysema
132
What is V_C?
VC = pulmonary capillary blood volume (gas has to find its way through the plasma) = 100 mL
133
What affects V_C?
↑during exercise due to capillary distension & recruitment of other capillaries in the lung
134
What is theta? What reduces it?
Θ = capacity of 1 ml of blood for O2 (gas has to combine with Hb) - Reduced in anemia
135
What is the transit time for a red blood cell in the pulmonary capillary bed?
V_c/C.O. = 1.2 sec
136
What is dissolved oxygen defined as?
Dissolved oxygen = oxygen in blood NOT bound to Hb
137
How do we calculate dissolved O2?
Amount of dissolved O2 = (Solubility) x (PO2)
138
What is the solubility of O2 in blood (IMPORTANT)?
Solubility of O2 in blood = 0.003 mL O2/(100 mL blood x mmHg)
139
How is dissolved O2 expressed?
Dissolved O2 can be expressed as, example, 0.3 mL O2/100 mL blood OR 0.3 vol%
140
Oxygen binds to Hb at what level?
1 gram of Hb binds 1.39 mL O2
141
What is oxygen capacity?
amount of oxygen bound to Hb per 100 mL blood when the Hb is fully saturated
142
How is oxygen capacity calculated?
Oxygen capacity = (g Hb/100 mL blood) x (1.39 mL O2/1 g Hb)
143
Is 1.39 mL O2/g Hb ever achieved? Why?
1. 39mLO2/gHb is a theoretical maximum that’s never met because:
1) Methemoglobin = when ferrous (F2+) has been oxidized to ferric (F3+) & can’t bind O2
2) Carboxyhemoglobin = when Hb binds CO
144
What is oxygen content?
actual amount of O2 bound to Hb plus dissolved O2
145
How is oxygen content calculated?
O2 content = (O2 capacity x Saturation) + (amount dissolved O2)
146
What is used to calculate percent saturation of hemoglobin with oxygen?
Given a PO2, one can use an oxyhemoglobin dissociation curve to determine the % saturation
For example:
Arterial blood has PO2 ~100 mmHg & Hb has 97% saturation
Mixed venous blood has a PO2 ~ 40 mmHg & Hb has 75% saturation
147
What is larger dissolved oxygen or bound oxygen?
Amount of O2 bound to Hb is much larger than that dissolved
148
Oxygen capacity refers to?
Oxygen capacity only refers to Hb & does NOT include dissolved O2
149
Oxygen content refers to?
Oxygen content refers to both the amount of O2 on Hb & the dissolved O2 (Even though it’s small)
150
What determines PO2?
Dissolved O2 is the only thing that determines PO2
151
What is the Bohr effect?
Bohr effect: ↑PCO2 in blood shifts the oxyhemoglobin dissociation curve to the right (less saturation for a given PO2)
152
What causes the Bohr effect?
Results from the fact that when CO2 is added to blood, both dissolved CO2 & H+ rise
1) H+ binds Hb & reduces the affinity of Hb for oxygen [primary reason]
2) CO2 forms carbamino compounds with Hb that reduce Hb’s affinity for O2
153
Describe effect of temperature on bound hemoglobin
increasing temperature shifts the curve to the right
154
Describe 2,3 DPG levels on the hemoglobin dissociation curve. Explain what happens at altitude
shifts the curve to the right
People at high altitude hyperventilate & blow off CO2, decreasing PCO2 & (Bohr effect)
causing the curve to shift left. Over time, levels of 2,3-DPG increase & the curve is
shifted back towards normal (not all the way & doesn’t overshoot)
155
What does right shift mean on a oxyhemoglobin dissociation curve?
Right shifts make it so that more O2 is made available for unloading into tissues (affinity of
Hb for O2 is decreased)
156
Describe what things cause right shift for hemoglobin curve
Summary: Increases in 2,3-DPG, dissolved CO2, H+ or temperature cause right shifts
(CADET face Right)
157
What is the rate limiting step in O2 consumption?
The rate limiting step is the cardiovascular system (transfer of O2 in blood)
158
Describe the body's relation to CO2
CO2 is a metabolic waste product that must be eliminated constantly; paradoxically, a steady-state level of CO2 must be retained in order to maintain acid-base status
159
Describe CO2 in the plasma
1. Dissolved CO2
2. Carbonic acid, H2CO3 (negligible)
3. Bicarbonate anion (HCO3-)
160
Describe CO2 in the red cell
1. Dissolved CO2
2. Carbonic acid, H2CO3 (negligible)
3. Bicarbonate anion (HCO3-)
4. Carbamino compounds (-NH2 +
CO2 -> -NH-COO- + H+)
161
CO2 makes what carbamino compound?
-NH2 + CO2 -> -NH-COO- + H+
162
CO2 composition in whole blood?
5% is dissolved CO2
5% is carbamino compounds
90% is bicarbonate anion
163
Describe the equilibrium of CO2 in the blood and lungs.
[eliminated by lungs] CO2(gas) ↔ CO2+ H2O (blood) ↔ H2CO3 ↔ H+ + HCO3
- [eliminated by kidneys]
164
HCO3 is eliminated by? CO2?
HCO3 is kidneys
| CO2 is lungs
165
CO2 is what type of gas?
CO2is a volatile acid (you can breathe it away as a gas)
166
Non-volatile metabolites are removed by?
Other acids produced by metabolism are nonvolatile & are eliminated by the kidneys
167
What are the units of measurement of CO2 in the plasma?
Vol% = mL of CO2 in all forms/100 mL of blood
Mmol/L or mM used to refer to CO2 in the plasma, especially when considering acid-base
problems; usually used to refer to specific forms of CO2 (i.e. mM dissolved CO2)
168
How is dissolved CO2 calculated?
Dissolved CO2 = solubility x PCO2
169
What is the solubility of CO2 in blood?
solubility of CO2 in blood = 0.0301mM/mmHg
170
What is PCO2 in arterial blood? Corresponding amount of dissolved CO2?
In arterial blood, PCO2 is approximately 40 mmHg so dissolved CO2 = 1.2 mM
171
Diffusion is driven by partial pressure or concentration?
Partial pressure (when going from liquid to gas or from liquid 1 to liquid 2)
172
Dissolved CO2 combines to form what?
Dissolved CO2 combines with water to form carbonic acid which dissociates to form H+ & HCO3
-
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3
-
173
What is the henderson hasselback equation?
pH=6.1+log([HCO3]/[CO2])
| pH=6.1+log([HCO3}/(0.0301 mM/mmHg *PCO2))
174
How does a blood gas machine work?
Inject sample into center compartment & a pH electrode measures pH
CO2 diffuses (H+ doesn’t); CO2 makes right side solution acidic (measured by pH electrode)
Oxygen diffuses into the left compartment that contains an oxygen electrode
175
What is the ratio of bicarbonate to CO2 in plasma?
[HCO3-]:[CO2] = 20:1
176
Normal PaCO2 is defined as?
Normal: (arterial) PaCO2 ~ 40 mmHg
177
Respiratory acidosis is defined as?
Arterial PCO2 > 45 mmHg
178
Effects of respiratory acidosis?
Concentrations of all compounds increase (CO2, H+, HCO3-); more CO2 = more acid
179
Causes of respiratory acidosis
Causes: anything that reduces ventilatory drive (1. Holding your breath, 2. Drug overdoses that
reduce ventilatory drive, 3. Obstructive lung disease)
180
What is respiratory alkalosis?
Arterial PCO2 < 35 mmHg; less CO2 = less acid thus alkalosis
181
Effects of respiratory alkalosis?
Concentrations of all components decrease (CO2, H+, HCO3-)
182
Causes of respiratory alkalosis?
Causes: 1. Hypoxic drive (ascent to high altitude) 2. Mechanical over-ventilation 3. Pain &/or
anxiety (“psychogenic hyperventilation”)
183
Describe the function of buffering in response to protons in blood
In the simulated respiratory acidosis, pH decreased & bicarbonate increased solely by added CO2 gas
CO2 + H2O ↔ H+ + HCO3
Some of the H+ remains free while most binds to blood buffers
184
Which is superior buffer, blood or plasma? Why?
Blood is a superior buffer compared to plasma, mainly due to blood buffers like Hb
In anemia, for a given increase in PCO2, the blood will become more acidic compared to normal
185
What is the haldane effect?
as oxygen is added to blood, CO2 is driven off
186
What is bohr effect?
as CO2 is added to blood, O2 is driven off Hb
187
How does the haldane effect occur?
1. When O2 binds to Hb, H+ ions are released
Hb-H+ + O2 -> Hb-O2 + H+
Then H+ + HCO3 -> CO2 + H2O (eliminated by lungs)
2. Hb forms fewer carbamino compounds in the presence of O2
188
Describe the relationship between O2 and CO2 according to Haldane
the lower the PO2, the lower the PCO2 needed to achieve the same blood CO2 content
189
Describe cardiac output to the lungs
The most important feature of the pulmonary circulation is that it receives the entire cardiac output
190
Describe the filter effects of the lung
The lung is a filter : lung sees the entire venous return & can remove particulate matter from the circulation
Physiologically : lung removes small emboli (blood clots) via proteases
Non-physiologically : dust/dirt/other particulate matter injected by drug users
191
Function of lung filter?
The filtration function of the lungs keeps the arterial circulation clear of particulate matter; cerebral & coronary circulations are particularly vulnerable to occlusions while it’s not serious if a small region of pulmonary circulation is blocked by particulate matter
192
Describe the metabolites/hormones affected by the lungs
```
Angiotensin I is converted to AII in one pass
Angiotensin II is untouched
Bradykinin is 80% removed in 1 pass
Serotonin is 90% removed in 1 pass
Epinephrine is not affected
Norepinephrine is up to 30% removed
```
193
Lung effect on angiotensin I
Converted to Angiotensin II in one pass
194
Lung effect on angiotensin II
No effect
195
Lung effect on bradykinin
80% removed in 1 pass
196
Lung effect on serotonin
90% removed in 1 pass
197
Lung effect on epi
Not effected
198
Lung effect on norepi
30% removed
199
Resistance and pressure in pulmonary circuit?
The pulmonary circulation is a low pressure/low resistance circuit
200
Describe pulmonary arterial pressure (values)
Pulmonary arterial pressure: 25 mmHg/8 mmHg (mean arterial pressure is 15 mmHg)
201
What is the mean pulmonary venous pressure
Mean pulmonary venous pressure is 2 mmHg & is virtually the same as left atrial pressure
202
Describe capillary pressures in the pulmonary circulation
Capillary pressures are in between; unlike systemic system, capillaries contribute significantly to the total pulmonary resistance & a lot of driving pressure from the right ventricle is dissipated across the pulmonary capillary bed
203
Describe pulmonary blood flow in the capillaries
Pulmonary blood flow is pulsitile in the capillaries & probably doesn’t impair gas exchange
204
What is pulmonary capillary resistance (values)?
Resistance is around 2-3 mmHg per L/min or about 10 fold less than systemic circulation
205
As CO increases, what happens to pulmonary resistance?
Pulmonary resistance decreases with increasing cardiac output; thus, pulmonary arterial pressure
does not increase substantially during exercise
206
How does pulmonary resistance decrease?
↓ in pulmonary resistance is a passive phenomenon due to (1) distention of the vessels
that are already well-perfused & (2) recruitment (opening up) of vessels not perfused
207
What is hypoxic vasoconstriction?
(unique to pulmonary circulation) -> pulmonary resistance increases with hypoxia
208
What happens to the lung in low PO2?
When lung is hypoxic (low PO2), arterioles constrict & pulmonary vascular resistance increases dramatically
209
What is the physiologic advantage to hypoxic vasoconstriction?
Major physiologic advantage: fetal lung there’s no need for blood to flow thru the pulmonary capillary
bed; fetal lung is hypoxic & high vascular resistance causes venous blood flow to the arterial circulation by:
A. the ductus arteriosus (pulmonary artery to aortic arch)
B. Foramen ovale (right atrium to left atrium)
o With 1st breath, O2 causes an immediate ↓in pulmonary resistance & blood flows immediately through lungs
210
Describe localized hypoxic vasoconstriction. Overall effect on the lung resistance?
If the hypoxia is localized, vessels (arterioles) constrict in that region; hypoxic vasoconstriction occurs only in that region & blood flow is re-directed to regions of the lung that have better ventilation
This localized vasoconstriction does little to increase pulmonary vascular resistance
211
Describe generalized hypoxic vasoconstriction. What does this lead to?
Generalized hypoxic vasoconstriction is seen most commonly in people living at high altitude
Vasoconstriction throughout entire lung & resistance of the entire pulmonary vasculature is ↑; thus,
pulmonary arterial pressure rises & there’s pulmonary hypertension resulting in a change in right ventricular structure (called Cor Pulmonale): dilation (acute phase) &/or hypertrophy (chronic
adaptation) of the right ventricle due to this increase in the resistance of the pulmonary vasculature
212
Describe the regional differences in lung ventilation
Regional Differences in Ventilation & Perfusion of the Lung
o In the lung, there’s less ventilation & perfusion at the apex of the lung compared to the base due to gravity
o Three Zone Model of Lung Perfusion (3 zones are called the “West Zones”)
213
Describe zone 1 (west zone)? Exist in humans?
Zone 1: apex (PA > Pa > PV)
No perfusion (perfusion pressure can’t overcome gravity)
Alveolar pressure > arterial & venous pressures = collapsed capillary
In humans, there’s just enough driving pressure from the right ventricle to overcome the force of gravity on the column of blood such that the apex is perfused & there’s probably no zone 1 in humans
214
Describe zone 2 (west zone)?
Zone 2: mid-region (Pa > PA > PV)
Arterial pressure is high enough to pump the blood up to this region
Arterial P > alveolar pressure = capillary is open (on the arterial side)
Venous pressure isn’t enough to maintain a column of blood from the heart up to Z2 so capillary constriction occurs towards the venous side
215
Describe zone 3 (west zone)?
Zone 3: base (Pa > PV > PA)
Both arterial & venous pressures exceed atmospheric pressures & no vessel collapse or constriction is seen
216
What is the respiratory quotient?
ratio of CO2 produced to O2 consumed; depends on what your body is burning for fuel
217
What is RQ for glucose? For Fat? Mixed?
Glucose : Ratio is 1
Fat Ratio is 0.703
People burn a mixture of sugars & fats so the RQ = 0.8
218
How is RQ measured?
Measure: pt breathes room air, collect exhaled gases, analyze for the amount of O2 removed & CO2 added
RQ = V_dot_CO2 / V_dot_O2
219
What is RQ?
CO2/O2 produced/consumed by tissues
220
Describe the effect of RQ on the alveolar air equation
Since O2 consumption per breath > CO2 production, have to accommodate for the O2 consumption in alveoli
221
Suppose the RQ = R = 1, PB = 760 mmHg, PIH2O = 47 mmHg, PIO2 = 150 mmHg & PIN2 = 563 mmHg...calculate the effect on pressures
If R = 1, PAH2O = 47 mmHg, PACO2 = 40 mmHg, PAO2 = 150-40 = 110 mmHg & PAN2 = 563 mmHg
Total = 760 mmHg
222
Suppose the RQ = R = 0.8, PB = 760 mmHg, PIH2O = 47 mmHg, PIO2 = 150 mmHg & PIN2 = 563 mmHg...calculate the effect on pressures
If R = 0.8, PAH2O = 47 mmHg, PACO2 = 40 mmHg, PAO2 = 150-50 = 100 mmHg & PAN2 = 563 mmHg
Total = 750 mmHg alveolar regions are subamospheric!
223
Effect of O2 diffusion into blood on alveolar air pressures
Since more O2 diffused into the capillaries than was replaced by CO2, alveolar regions are subatmospheric
224
Describe what happens to account for the alveolar depletion of O2 when RQ doesnt equal 1. What is used?
To respond to the pressure drop, the alveolar regions being in more fresh air (passively) from the airways
o The flow in will be 2 parts O2 & 8 parts N2, which will restore alveolar pressure to Patm
o The subatmospheric pressure was caused by diffusion of O2 into the blood & was replaced by a
combination of mostly N2 & some O2
225
If RQ=1 or FIO2 is 100% what is PAO2?
PAO2 = PIO2 – PACO2
226
If FIO2 is 21% or RQ =0.8 what is PAO2?
PAO2 = PIO2 – PACO2 x 1.2
227
How is PIO2 calculated?
PIO2 = (PB – 47 mmHg) x FO2
228
What is arterial hypoxemia?
abnormally low PO2 in the arterial blood (low PaO2)
229
Do people with anemia have arterial hypoxemia?
Note: people with anemia (low Hb) do NOT have arterial hypoxemia; they have a normal PaO2
230
What are the major causes of arterial hypoxemia?
Causes: (1) hypoventilation, (2) diffusion limitation (3) shunt (4) ventilation-perfusion mismatching
231
What is the alveolar-arterial oxygen difference? Typical value?
A-a difference = PAO2 – PaO2 should be low since O2 normally equilibrates
232
What is the alveolar ventilation equation?
V_dot_A = 863 x V_dot_CO2/PaCO2
233
What happens if CO2 production doubles, according to the alveolar ventilation equation?
States that if your CO2 production doubles, you must double alveolar ventilation to maintain constant PaCO2
234
Hypoventilation is the same as? Defined by?
same as respiratory acidosis: Defined as PaCO2 > 45 mmHg
235
When PAO2 decreases, what happens to Hb saturation? Why?
PAO2 decreases; Hb saturation is lower because
(1) PaO2 can’t be higher than PAO2
(2) The acidosis (from the CO2) shifts the O2-Hb dissociation curve to the right
236
What causes hypoventilation?
(1) reduced ventilatory drive (2) obstructive lung disease (3) mechanical underventilation
237
What are the 3 major features of hypoventilation as an arterial hypoxemia?
1. PaO2 lower than normal (by definition)
2. PaCO2 > 45 mmHg
3. A-a difference normal (O2 normally equilibrates between alveolar gas & arterial blood)
238
What is diffusion limitation arterial hypoxemia? When is it seen?
least common of arterial hypoxemias; mostly seen in emphysema & pulmonary fibrosis
239
What causes diffusion limitation arterial hypoxemia?
low diffusing capacity of the lung (as measured by DLCO)
240
Describe the physiology of diffusion limitation
Diffusion limitation occurs when the RBC is not fully oxygenated by the time it leaves the pulmonary capillary. At rest, the transit time of a RBC in the pulmonary capillary is about 1 sec & normally oxygenation is complete in 0.2-0.3 secs. In a diffusion limitation, oxygenation isn’t completed during the transit period.
There’s a small percentage of Hb that should have been loaded with O2 but was not
241
What are the 3 features of diffusion limitation arterial hypoxemia?
1) A substantial alveolar-arterial oxygen difference (O2 doesn’t equilibrate)
2) Alveolar-arterial oxygen difference is eliminated with elevated inspiration
3) Diffusion limitation is much more severe with exercise due to shorter transit time & lower Hb
saturation in venous blood
242
What are shunts?
a pathway thru which venous blood enters arterial circulation without any gas exchange whatsoever
243
How are shunts reported quantitatively?
Usually reported as a percentage or fraction of the cardiac output: Q*S/Q*T (shunt/C.O.)
244
Describe the physiologically normal shunts
Normal shunts: Thebesian veins (drain into L ventricle) & bronchial circulation (drain into pulmonary vein)
245
What are two examples of abnormal shunts?
Abnormal shunts: (1) Pulmonary edema (“pulmonic shunts”) [blood flows but no oxygen because alveoli are closed off] & (2) Septal defects (“right-to-left shunts”)
246
Describe the most distinguishing factor of shunt arterial hypoxemia
1. Alveolar-arterial oxygen difference is high with room air
| 2. A-a oxygen difference is enormous when breathing elevated inspired air (such as 100% oxygen)
247
Describe the reason why A-a oxygen difference is high in shunt arterial hypoxemia
Suppose that
o (a) patient has a 10% shunt [for every 100 mL of cardiac output, 90 mL comes from the lungs (oxygenated) &
10 mL comes from the shunt (not oxygenated)],
o (b) PB = 760 mmHg
o (c) Oxygen capacity of the blood is 20 vol% & the person breathes 100% O2
Patient is now given 100% oxygen to breathe…
For every 100 mL of blood flow, 90 mL is passing through the lungs & receives oxygen
o PAO2 = (PB-47)x1-PaCO2 = (760-47)x1-40=673 mmHg
o Hb becomes 100% saturated with oxygen (anytime the PaO2 > 150 mmHg, we consider Hb saturation 100%)
o Dissolved O2 = 0.003x673 = 2mL O2/100 mL blood or 1.8 mL O2 per 90 mL blood
For every 100 mL of blood flow, 10 mL is passing through the shunt & doesn’t receive O2
o Hb is 75% saturated (same as mixed venous blood)
o Dissolved O2 is negligible (relative to the amount of dissolved oxygen in the blood coming from the lungs)
o O2 capacity is 20 mL O2/100 mL blood, but we’re considering 10 mL so O2 capacity is 2 mL O2/10 mL blood
o Since Hb saturation is 75%, it means that Hb has 1.5 mL O2 on it & an 0.5 mL O2 is needed to fully saturate
1.8 mL dissolved O2 from lung blood mixes w/ negligible dissolved O2 from shunt blood
The result is 100 mL
o 0.5 mL of dissolved O2 from the blood from the lungs is used to saturate the Hb in the blood from the shunt
o Dissolved O2 left per 100 mL is 1.8-0.5 = 1.3 mL
o PaO2 = dissolved O2/0.003 = 1.3/0.003 = 433 mmHg
o A-a difference = 673 mmHg – 433 mmHg = 240 mmHg
Some of the dissolved oxygen coming from the oxygenated blood is used to saturate the Hb coming from the shunted
blood; it’s only dissolved O2 that determines the PO2 in blood so when dissolved O2 is used to oxygenate Hb, the PO2
falls & leads to the substantial alveolar-arterial difference
248
What are the major features of ventilation-perfusion mismatching?
1) A large alveolar-arterial O2 difference breathing room air
2) Corrected by increasing the PIO2
249
Give two examples of ventilation-perfusion mismatching
Ventilatory: Obstructive lung disease (because airway obstruction is rarely uniform), regional
differences in compliance
Circulatory: Pulmonary embolism
250
What is the most common cause of ventilation-perfusion mismatching?
Most common cause: aging
A young adult will have an Alveolar-arterial O2 difference approximately 5
An old adult may have an Alveolar-arterial O2 difference approximately 20
This is not usually a cause for concern
251
What is the ventilation-perfusion ratio?
(V*A/Q*) = ratio of the rate of alveolar ventilation to pulmonary blood flow
*=dot
252
What are the normal values for the ventilation-perfusion ratio?
Normally, V*A = 4 L/min & Q* = 5 L/min so V*A/Q* is normally 0.8
253
Describe the ideal O2 and CO2 exchange
Ventilation & perfusion matching is important to achieve ideal O2 & CO2 exchange; usually, the ventilation perfusion
ratios throughout the lung are close to the overall ventilation-perfusion ratio of 0.8
254
Give examples of V-P mismatch (the overall as well as extremes)
Region of lung is well ventilated but poorly perfused: V*A/Q* = [3 L/min]/[1 L/min] = 3
Region of the lung that’s poorly ventilated & well perfused: V*A/Q* = [1 L/min]/[4 L/min] = 0.25
But overall: V*A/Q* = [3 L/min+1 L/min]/[1 L/min+4 L/min] = 4/5 = 0.8
255
Describe what happens with no ventilation in arterial hypoxemia (ventilation-perfusion mismatch)
No ventilation such that V*A/Q* = 0 (a shunt)
If there’s no ventilation, the air inside the alveolus (if it hasn’t collapsed which it usually does) will have the same partial pressures as the mixed venous blood passing through the pulmonary capillary
For example, PAO2=40 and PACO2=45 and so do blood partial pressures (P_Vdot)
256
Describe what happens with no perfusion in arterial hypoxemia (ventilation-perfusion mismatch)
If there’s no perfusion, then the air inside the alveolus will have the same partial pressures as the inspired gases in the airways
E.g. PIO2=150 and PICO2=0 and blood matches
257
Describe a normal alvelous in terms of ventilation perfusion matching. What are the values?
If there is both ventilation & perfusion, the alveolus will have gas partial pressure in between that of the inspired gases and the gases in the mixed venous blood. The exact values are determined by computer simulation/numerical approximations.
PIO2=150 PICO2=0
PAO2=100 PACO2=40
P_VdotO2=40 P_VdotCO2=45
258
Describe what happens when the ventilation perfusion ratio increases
As the ratio of ventilation to perfusion increases, the partial pressure of CO2 in the alveolus falls & the partial pressure of O2 rises
259
Describe the physiological response to ventilation perfusion mismatch
In a ventilation perfusion mismatch, you see both poorly ventilated regions (Low VQ ratio) & well ventilated regions (High VQ ratio) because total ventilation must remain the same in order to maintain a normal PaCO2 CO2 is retained in the poorly ventilated regions & extra amount of CO2
“blown off” in the well-ventilated region
260
Describe CO2 and O2 levels resulting from ventilation perfusion mismatch
1) A well-ventilated region of the lung can
compensate for the abnormal accumulation of CO2 in a poorly-ventilated region (linear curve)
2) A well-ventilated region of the lung
cannot compensate for the abnormal loss
of O2 in a poorly ventilated region (non-linear curve)
261
Describe CO2 as a chemical factor in blood with regard to ventilation
CO2 : mainly dissolved CO2, not bicarbonate/carbamino compounds (ventilation is sensitive to PaCO2)
Hypercapnia = elevated PaCO2
262
Describe O2 as a chemical factor in blood with regard to ventilation
O2 : In particular, dissolved O2 not oxygen bound to Hb (thus, the rate of ventilation is sensitive to PaO2)
Hypoxia = reduced PaO2
263
Describe pH as a chemical factor in blood with regard to ventilation
(acidosis = reduced pH)
A) from CO2 in a respiratory acidosis
B) from non-volatile acids in a metabolic acidosis (lactic acid, diabetic ketoacidosis)
264
What are central receptors?
Central receptors usually referred to as the ”Chemosensitive Area of the Brain” (CSA) aka Central chemoreceptor, aka CO2 chemoreceptor; located in the medulla
265
Where is the CSA located? How does it work?
The CSA is located on the brain side of the blood-brain barrier, but senses dissolved CO2 in the blood
The dissolved CO2 diffuses across the blood brain barrier (but not H+ or bicarbonate)
Once in the CSF, the CO2 combines with water to form H+ & HCO3
Data indicates that it’s the H+ that binds in the CSA to regulate ventilation; but, note, that H+ isn’t
coming from the blood but from the dissolved CO2 that diffuses across the blood-brain barrier
266
What is the peripheral receptor in humans?
Carotid bodies
267
The carotid bodies account for?
1) All ventilatory response to low PaO2 (hypoxic drive)
2) About ¼ of the response to changes in PaCO2
3) All the response to changes in pH in a metabolic acidosis/alkalosis
268
Why are carotid bodies well suited for measuring arterial blood?
The carotid bodies are particularly well suited to sense arterial blood partial pressures because the rate of blood flow is very high relative to metabolism; this means that the partial pressure of, for example, oxygen is similar in both the arterial blood & the venous blood of the carotid or
PaO2 PVO2
This means that the carotid body is bathed with dissolved O2 that is essentially equal to PaO2
269
Describe the response to CO2 increase
Essentially, if PaCO2 rises, ventilation rises to compensate & does so quite
dramatically
The ventilatory rate increases almost 2x per mmHg rise in PaCO2
Ventilatory responses serve to keep the PaCO2 within a few mmHg of the set point (at sea level, 35-40 mmHg)
270
What is the CO2 set point?
Ventilatory responses serve to keep the PaCO2 within a few mmHg of the set point (at sea level, 35-40 mmHg)
This is achieved via ventilation modification
271
When is response to hypoxia triggered?
occurs significantly when PaO2 falls below about 60-70 mmHg
Sensed by carotid bodies
272
What is del V_40?
ΔV40 = difference in ventilatory rate when the PaO2 is 40 mmHg vs. a PaO2 of 150 mmHg
273
What is hypoxic drive?
hyperventilation, a ventilatory rate faster than that needed to maintain a normal PaCO2
274
What results in the alveolus due to hypoxic drive?
Alveolar ventilation ↑ due to the hypoxic drive & thus PaCO2 ↓due to hyperventilation (blow off CO2)
275
Describe the mathematics of hypoxic drive step by step from AV equation to result in PAO2
AV equation: PaCO2=V*CO2/V*A * 863
To decreases PaCO2, we increase V*A
PAO2=PIO2-PaCO2x1.2
Decrease in PaCO2, increases PAO2
276
What are the physiologic advantages to the rise of PAO2 in hypoxic drive?
1) It raises the arterial oxygen (PaO2) & increases Hb saturation
2) It reduces hypoxic vasoconstriction
277
Describe acute hypoxic drive
1. Hypoxia stimulates neural activity at the carotid body causing an increase in ventilatory rate
2. Hyperventilation ↓ PaCO2, making the CSF pH more alkaline causing CSA to ↓ventilatory rate
Thus, from the carotid bodies, a signal to ↑ ventilation & from the CSA a signal to ↓ ventilation
Net result: a small increase in ventilatory rate in the acute stage (first 24 to 48 hours)
278
Describe chronic adjustment to hypoxic drive
1. Over hours/day, the pH of the CSF is restored toward normal by a reduction of bicarbonate
pH=6.1+log([HCO3]/(0.0301xPCO2))
Decrease PCO2 has to have corresponding increase in bicarbonate to maintain pH
2. The result: the signal from the carotid bodies to increase ventilation is unopposed by a signal
from the CSA & the full effect of hypoxic drive is felt (chronic higher ventilatory rate)
279
What is respiratory acidosis? Response?
Respiratory acidosis = increase in CO2
The increase in PaCO2 increases [H+] of the CSF causing an increase in ventilatory rate
Increase in [H+] of the blood stimulates carotid body activity causing an increase in ventilatory rate
Result: ventilatory stimulation from both the carotid bodies & the CSA
280
What is metabolic acidosis? Response?
Metabolic acidosis = increase in acids from other sources (e.g. lactic acid, diabetic ketoacidosis)
Same acute/chronic phases seen in hypoxic drive & for the same reasons
281
Describe acute phase of metabolic acidosis repsonse
1. Low pH stimulates neural activity at the carotid body & causes an ↑ ventilatory rate
2. Hyperventilation ↓PaCO2 making the CSF pH more alkaline & causing a ↓ ventilatory rate.
Net result: a small increase in ventilatory rate in the acute stage
282
Describe chronic adjustment to metabolic acidosis
1. pH of the CSF is restored towards normal (via bicarb)
2. Inhibition of ventilatory rate from the CSA becomes insignificant
3. The stimulus from the carotid bodies (due to the ↑ in blood [H+]) causing an increase in
ventilatory rate is unopposed by the CSA & higher ventilatory rate is observed chronically
283
What is the equilbirum expression for CO2-Bicarbonate?
CO2+H2) H2CO2 H+ + HCO3-
284
What is the ratio of CO2:H2CO3:HCO3-?
340:1:6800
285
Can we ignore carbonic acid at pH 7.4
Yes, very small component of total products
286
What is Ka' defined as?
Ka'=[H+][HCO3-]/[CO2]
Not that Ka'=Ka*[H2O]
287
What is the numerical value of Ka'?
800 x 10^-9 M
288
What is normal concentration of H+?
40 nM
289
What is normal concentration of HCO3-?
24 mM
290
What is normal concentration of CO2?
1.2 mM
291
If we increase hydrogen ions in the body via a metabolic acid, what happens?
Increase in hydrogen is countered by decrease in bicarbonate (combines) and production of CO2
(Use quadratic formula e.g. -X for protons and bicarb, and +X for CO2 and use Ka')
292
Why is CO2 ventilation a better buffer system that closed?
Removing CO2 created by acid challenge via ventilation results in less new hydrogen ion level and therefore a more normal pH (bicarb levels are approximately the same)
293
What is PCO2 isobar?
PCO2 is maintained by CO2 blow off and therefore the change in bicarb as a function of pH is very vertical
294
How do we calculate the PCO2 isobar?
Calculate pH from Ka'=[H+]{HCO3]/[CO2]=800 nM
1. Initial conditions:
[H+] = 40 nM, [HCO3-] = 24 mM, [CO2] = 1.2 mM
2. Choose an amount of H+ to add
3. Using previous analysis, solve for new H+ & pH
4. Solve for the new [HCO3-]
5. Plot [HCO3-] (y-axis) vs. pH (x-axis)
Use HH equation pH=6.1+log([HCO3]/(0.03018*PCO2))
1. Select a constant PCO2
2. Choose various concentrations of bicarbonate
3. Use the equation to solve for pH
4. Plot these x, y pairs (pH & [HCO3-] on the pH-bicarbonate diagram
295
Describe PCO2 isobars if strong acid or base added to system
If a strong acid or base is added & ventilation
keeps PCO2 constant, the new pH & [HCO3-] will
be on the same PCO2 isobar
296
What happens if PCO2 changes to a PCO2 isobar?
If PCO2 changes, new values of pH & [HCO3-] will be somewhere on a different isobar
Where that somewhere is depends on the other
body buffers
297
Why does the body have other buffer systems from the CO2-bicarb?
We need other buffer systems because CO2 cannot buffer itself
If you add more CO2, then you need other buffers to remove H+ without regenerating the CO2
298
What happens in a metabolic acid challenge (not CO2)?
results in addition of H+, equilibrium shifts to the right & excess CO2 is removed by ventilation (blown off)
299
How does the body respond to respiratory acid challenge (CO2) (assume only CO2 bicarb system)?
Respiratory (CO2) acid challenge without other buffers results in the addition of CO2 & not much else happening such that the pH is unacceptably acidic
300
If there were no other buffer systems, what would happen?
CO2 is constantly generated by tissues & carried away by the venous circulation to the lungs; if this was the only buffer system, the blood would be very acidic
301
Describe generally what happens with other buffer systems responding to CO2 increase
When CO2 levels increase, H+ ions that are generated combine with other body buffers & pulls the CO2-bicarbonate equilibrium to the right such that most of the CO2 introduced into the system is carried away as
bicarbonate
o CO2 + H2O HCO3- + H+ ( body buffers)
o Other buffers are needed to (1) buffer H+ ion produced by excess CO2 & (2) carry CO2 as HCO3- & not dissolved CO2 (pull the equilibrium to the right)
302
What are the body's other buffer systems?
1. Phosphate: H+ + HPO4 ↔ H2PO4
2. Plasma protein: H+ + (Protein) ↔ (Protein-H+)
3. Red Cell
4. Other cells
5. Bone buffering
303
Red Cell buffers?
buffers CO2 only & does not buffer non-volatile acids
o Note: Volatile acid = CO2; nonvolatile acids = fixed acids
304
How does Red Cell buffer?
A. Dissolved CO2 enters the RBC
B. Some CO2 remains as dissolved CO2
C. Some becomes carbamino compounds (combines with Hb, H+ ions released & buffered by Hb)
D. Most dissociates to become H+ and HCO3- (first converted by carbonic anhydrase to carbonic
acid & then immediately dissociates)
H+ is buffered by Hb
HCO3- diffuses out in exchange for chloride (“chloride shift)
Net result: the CO2 produced by metabolism is carried as HCO3- & carbamino compounds
305
What is the chloride shift?
HCO3- diffuses out in exchange for chloride in red cell buffering
306
How do other cells buffer?
Buffer H+ generated both by CO2 & non-volatile acids; either:
A. H+ enters the cell & a Cl- follows to maintain neutrality
B. H+ enters the cell & a Na+ or K+ leaves
o This can lead to an elevation in K+ in the extracellular fluid (hyperkalemia)
307
Why does other cell buffering lead to hyperkalemia?
H+ enters the cell & a Na+ or K+ leaves
308
Describe bone buffering
Calcium-CO3-Na + H+ + Cl- ↔ Calcium-Cl + Na+ + HCO3
309
Compare Buffering of CO2 vs. buffering of non-carbonic acid
In response to strong acid (metabolic acidosis), most of the buffering is carried out by CO2-bicarb (<50%) system and cellular buffers; there’s no red cell buffering
In response to elevated CO2 (respiratory acidosis), there’s no CO2-bicarb buffering & mainly cellular buffering (red cell buffering (~30%))
310
Other cells buffer what insults?
CO2 and non-volatile acids
311
Describe the time course of buffering
Extracellular fluid or ECF (misnamed because it includes the RBC)
A. Plasma & RBC: seconds to minutes
B. Interstitial fluid: 10 – 30 minutes
o Cellular compartments (other than the RBC): 2-4 hours
o Bone: hours – days
o Kidney: days
312
What does extracellular fluid include as buffer? How fast do these systems respond?
A. Plasma & RBC: seconds to minutes
| B. Interstitial fluid: 10 – 30 minutes
313
What is a buffer value?
the body’s ability to buffer a CO2 challenge
314
Buffer value is equal to? Units
Buffer value = Delta_HCO3/Delta_pH
Units mmol/L/pH aka. slyke (sl)
315
High buffer value means?
High buffer value (a good thing): when CO2 rises, large amounts of HCO3- are formed & the pH changes little
316
Low buffer value means?
Low buffer value (a bad thing): when CO2 rises, HCO3- changes little & pH becomes more acidic
317
Buffer value denotes what? What is being buffered?
Buffer value is the ability of body buffers OTHER THAN CO2-BICARB to
1) bind H+
2) convert CO2 to HCO3- by pulling the equilibrium to the right
318
What are the buffer values for plasma, whole blood, ECF?
```
Plasma (poor buffer): 4 mmol/L per pH unit
Whole blood (good buffer): 25 mmol/L per pH unit ECF = plasma (poor) + RBC (good) + interstitial fluid (poor) = 11 mmol/L per pH unit
```
319
What is a buffer line?
Buffer value on the pH-bicarbonate diagram (the “buffer line”)
Buffer value = ΔHCO3- = -(buffer value) x ΔpH [note: this is y = (slope)(x)]
The ECF line is the most important for acid-base problems
320
Describe the sequence of events in retention of CO2
Suppose a person retains CO2 & PCO2 begins to rise: During the first 10-30 minutes, the increasing acidity equilibrates with the blood/interstitial fluid & the change in pH & bicarb follow the ECF buffer line During the next several hours, H+ equilibrates with the intracellular space & pH/bicarb change according to a new buffer line
Over the next 24 hours or so, (1) buffering by bone takes place & (2) kidney retains HCO3- to
change pH toward normal
321
Describe what happens to the buffer line over time for CO2 retention
Becomes more vertical i.e. pH is stablized and bicarb levels matter less (no effect on pH)
322
What is the normal range of acid-base for arterial blood?
o pH 7.35 to 7.45
o PCO2 35 to 45 mmHg
o HCO3- 22 to 26 mmHg
323
When does acid-base disorder occur?
1. There is a respiratory &/or renal abnormality
| 2. Acid/base load exceeds the capacity of the respiratory &/or renal system to handle it
324
What is the clincial term for pH outside of normal range?
acidemia (lower than normal) & alkalemia
| higher than normal
325
What is respiratory acid-base disorder?
When the initial (“primary”) abnormality is a change in PCO2, it’s called respiratory acidosis
(hypoventilation) or respiratory alkalosis (hyperventilation)
326
What is metabolic acid-base disorder?
When the initial (primary) abnormality is due to (1) a gain/loss of non-carbonic acid (non-volatile acids) or
(2) a gain/loss of bicarbonate, it’s called metabolic acidosis or metabolic alkalosis
327
What is compensation? What happens?
When a primary acid-base disturbance occurs, a compensatory change occurs (called “compensation”) that restores the pH towards normal but not all the way.
o Either the PCO2 or the bicarb or both will become further away from the normal value as a result
o [H+] = 800 nM*[CO2]/[HCO3]
If the primary abnormality is an increase in CO2 (↑ PCO2), compensation is to increase bicarb
If the primary abnormality is a decrease in bicarbonate, then compensation is to decrease PCO2
328
What happens in metabolic acidosis generally?
Ded pH
Inc [H]
Distrubance is Dec [HCO3]
Compensation Hyperventilation to dec PaCO2
329
What happens during metabolic alkalosis generally?
Inc pH
Dec [H]
Distrubance is Inc [HCO3]
Compensation Hypoventilation to inc PaCO2
330
What happens during respiratory acidosis generally?
Dec pH
Inc [H]
Disturbance is Inc PaCO2
Compensation is Inc HCO3 by inc reabsorption
331
What happens during respiratory alkalosis generally?
Inc pH
Dec [H]
Disturbance is Dec PaCO2
Compensation is Dec HCO3 by Dec reabsorption
332
What is the primary disorder of metabolic alkalosis?
(1) more alkaline pH (2) increase in bicarbonate
333
What is the compensation for metabolic alkalosis
Increase PCO2 via hypoventilation
334
What causes metabolic alkalosis (3)?
A. GI loss of H+
B. Hypokalemia
C. Contraction alkalosis
335
What is GI loss of H+?
In normal digestion, elevation of bicarbonate is transient because the pancrease then secretes bicarb to neutralize gastric acid in the small intestine
Excessive secretion of H+ into the lumen leads to excessive accumulation of bicarb in the
plasma
Alkalosis occurs as the result of vomiting
336
Why does hypokalemia cause metabolic alkalosis?
K+ leaves the cell to restore [K+] to normal & so H+ enters the cell in exchange such that the ECF becomes alkaline
337
What is contraction alkalosis?
both salt (NaCl) & water are lost but not HCO3-
Usually occurs more commonly with diuretics
Causes contraction of ECF & so the concentration of bicarb increase (same amount but now in a smaller volume)
Maintaining volume takes priority over maintaining pH & the kidney saves bicarbonate in
order to maintain volume
338
Describe the acute phase for metabolic alkalosis response
1. Carotid body senses alkalosis & signals a decrease in ventilatory rate
2. Chemosensitive area of the brain (CSA) senses the increase in PCO2 & signals an
increase in ventilatory rate
Net: small decrease in ventilation
339
Describe the chronic phase response to metabolic alkalosis
over time, the pH of the CSF is rest & more hypoventilation occurs (signal from thecarotid is unopposed by signals from the CSA)
340
What limits hypoventilation in metabolic alkalosis?
Hypoxic drive ultimately limits the magnitude of the hypoventilation
Recall: PAO2 = PIO2 – PaCO2 x 1.2
Once PaO2 falls below about 70-80 mmHg, hypoxic drive occurs & prevents further hypoventilation
341
What is the primary disorder of metabolic acidosis?
(1) more acid pH (2) decrease in bicarb
342
What is the compensation for metabolic acidosis?
decrease PCO2 (hyperventilation)
343
What are the three causes of metabolic acidosis?
A. Inability to excrete dietary H+ usually due to renal disease
B. Increased H+ load (lactic acidosis or diabetic ketoacidosis)
C. Bicarbonate loss (diarrhea, renal disease)
344
What is the plasma anion gap? Normal range?
Plasma anion gap (no relation to urinary anion gap) = [Na+] – ([Cl-] + [HCO3-])
Normal range: 8 to 16 nM
345
What is hyperchloremic acidosis?
metabolic Acidosis with NO CHANGE in anion gap (ex. Infusion of HCl)
346
Describe the physiology of hyperchloremic acidosis
With buffering by the CO2-bicarbonate system, this results in a 1 for 1 replacement of bicarbonate (lost) with chloride (gained)
Physiological examples: in diarrhea or renal disease, where NaHCO3 is lost, the kidney saves NaCl to maintain extracellular fluid volume
347
Describe metabolic acidosis with increase in ion gap
when bicarb is replaced by an “unmeasured” anion
Ex. Lactic acidosis
MUDPILES: Methanol, uremia, diabetic ketoacidosis, paraldehyde/propylene glycol,
infection/ischemia/isoniazid, lactate, ethelyene glycol/ethanol & salicylates/starvation
348
What is MUDPILES?
Methanol, uremia, diabetic ketoacidosis, paraldehyde/propylene glycol,
infection/ischemia/isoniazid, lactate, ethelyene glycol/ethanol & salicylates/starvation
Leads to metabolic acidosis with increase in anion gap
349
How does metabolic acidosis resolve?
increase in plasma bicarb without a corresponding increase in H+
1. Administer NaHCO3 adds bicarb w/o an associated H+
2. Physiologically, the kidney must restore normal bicarbonate levels (secretion of excess H+ in urine)
350
What is the primary disorder of respiratory acidosis?
Primary disorder (1) more acid pH (2) increased PCO2/increased [HCO3]
Due to hypoventilation
351
Describe compensation to respiratory acidosis
Primary event (retention of CO2) causes a (small) increase in plasma bicarbonate & the
compensation by the kidney also causes increased bicarb; however, the primary event is
accompanied by an increase in H+ caused by CO2 retention.
The compensation is not accompanied by an increase in H+ because the kidney secretes the H+ in the urine
352
What are the causes of respiratory acidosis?
Ventilation not appropriate for the level of CO2 production; PCO2 rises to a higher steady-state level
A. Inapproproate control of ventilation
B. Obstructive lung disease
C. Chest wall &/or muscle disorders
D. Pulmonary fibrosis
353
Describe the acute phase of respiratory acidosis
```
Acute stage (10-30 min): change in pH & HCO3- follows the ECF buffer line on the CO2-bicarbonate
diagram
```
354
Describe renal compensation to respiratory acidosis
Renal compensation: increase in PCO2 stimulates H+ secretion into the lumen & new bicarbonate that’s created as a result enters the plasma
355
When is respiratory acidosis most commonly seen?
Most often seen in chronic obstructive lung disease (smokers) & pulmonary fibrosis
356
What is the primary disorder of respiratory alkalosis?
(1) more alkaline pH (2) decreased PCO2/decreased [HCO3-]
Hyperventilation
357
Describe compensation to respiratory alkalosis
over several days, the kidney decreases plasma bicarbonate further
Primary event (reductive of CO2) causes a (small) decrease in plasma bicarbonate; compensation by the kidney also causes a (much larger) decrease in bicarbonate that moves pH back toward normal
primary disturbance is ↓PCO2 & compensation (renal) is ↓[HCO3-]
358
What are the causes of respiratory alkalosis?
1. Hypoxia (hypoxic drive)
| 2. Stimulation of respiratory center (pain, anxiety) 3. Mechanical overventilation
359
Describe the acute phase of respiratory alkalosis
rise in pH & fall in HCO3- follow the ECF buffer line
360
Describe renal compensation in respiratory alkalosis
fall in PCO2 causes the kidney to retain H+ & eliminate HCO3- in the urine (about 5 mM fall in bicarb for each 10 mmHg call in PCO2)
361
How to tell what type of acid-base imbalance?
First, look at pH (alkalosis or acidosis?)
Then look at bicarbonate (metabolic or respiratory?)
Metabolic:
What’s the appropriate compensation?
Is the compensation occurring?
Respiratory:
Is the value on the ECF buffer line? If yes, it’s
acute. If no, it’s chronic (cellular buffering, bone
buffering & renal compensation)
362
Describe the levels and compensation for metabolic alkalosis
```
PaCO2 = 52 mmHg; HCO3- = 38 mM; pH = 7.49
pH = alkalosis; bicarbonate puts in quadrant for metabolic alkalosis (just example numbers)
```
Appropriate compensation is hypoventilation & yes, it’s happening, because PaCO2 is above normal
363
Describe the levels and compensation for metabolic acidosis
```
PaCO2 = 25 mmHg; HCO3 = 10 mM & pH = 7.22
pH = acidosis; bicarb = metabolic acidosis
```
Appropriate compensation is hyperventilation which is occurring because PaCO2 is below normal
364
Describe the levels and compensation for respiratory alkalosis
```
PaCO2 = 23 mmHg, HCO3 = 21.8 mM & pH= 7.6
pH = alkalosis; bicarb puts in quadrant for respiratory alkalosis
```
On the ECF line so acute respiratory alkalosis (no renal compensation yet)
ECF line recall is Bicarb ~ -11*pH
365
Describe the levels and compensation for respiratory acidosis
```
PaCO2 = 75 mmHg; HCO3 = 35 mM & pH = 7.29
pH = acidosis, bicarb in respiratory alkalosis quadrant
```
Not on the ECF line so chronic respiratory acidosis
