Pulmonary Biochemistry Week 2 Flashcards
What are the three processes for gas exchange?
ventilation, gas exchange across barriers, perfusion or blood flow
The ______ pH is the pH of the blood and is easily measured
intravascular
What is normal pH for the human body?
7.4; range is 7.35 and 7.45
What is the normal [H+] range in the human body?
40 nM, range between 35 and 45 nm
Life is sustainable within what [H+] ranges
16 nM and 16 nM [H+]
Does the intracellular pH equal the extracellular pH?
No, maintain an imbalance on purpose (intracellular is 7, extracellular is 7.4)
True/False: Acid production originates extracellularly
False, intracellular
The concentration of buffers is 3X higher in the ICF than ECF
True
True/False - Protons freely flow across membranes
FALSE - protons are charged and need active exchangers. This is what Na/H and K/H exchanges are for.
Every acid in the body uses the same H+ ions and they are therefore coupled to one another. This is known as the _______
isohydric principle.
If the collecting ducts of the kidney contain urine at ph=5, what is the [H+] differential between normal blood and the described urine?
Normal blood is 7.4. Therefore difference is 10^2.4 = urine contains 252X more [H+] than blood
When are buffers at their highest capacity?
when at highest concentration and their pKas are closer to the working pH (pH of environment)
What are the three main NON-VOLATILE buffers in ECF?
hemoglobin, plasma proteins, phosphates [in order of buffer capacity]. NOT NH4+ BC TOXIC TO BRAIN
What is the volatile buffer system in the in the ECF? Why is it considered volatile?
bicarbonate, because CO2 gas is involved
Which non-volatile buffer has the highest capacity and why?
hemoglobin because of the abundant histidine side chains and high concentration; 20% of capacity!!!
Hemoglobin is found intracellularly. Why is it considered an extracellular buffer then?
It is found inside RBCs which are permeable to H+ ions. Hgb has a rapid impact on ECF and therefore considered an ECF buffer.
_______ is the most plentiful plasma protein
Albumin
At a concentration of 1mM, _____ is not as important of a buffer in the ECF than in the renal tubular filtrate
phosphate
Non-volatile buffers mitigate pH changes due to changes in _______
volatile acid (CO2)
True/False: Bicarbonate system can mitigate pH changes due to changes in CO2 in the ECF
FALSE -BICARBONATE DOES NOT BUFFER INCREASES IN CO2
What is the most powerful buffer of the ECF?
BICARB!
True/False: CO2 can go across membranes freely
True
How is a manometer used to measure mmHg?
Have U-shaped manometer, put vacuum on one side and measure height of column on other side
True/False: Composition (fractional combination of all gases) in the air is the same at any altitude.
TRUE
What does change according to altitude?
The barometric pressure [pressure of all gases in air]
What is the Pb in Reno?
680 mmHg.
________ is the pressure that the gas would have if it alone occupied the volume
partial pressure
How do you obtain relative vs absolute concentration of a gas?
relative is partial pressure, absolute is via PV=nRT equation
True/False: In environment, PCO2 is so low that it is clinically considered zero
True
What is the PO2 fraction in environment?
21%
The partial pressure of a gas dissolved in a liquid is _______ the partial pressure of gas above the liquid
equal to
The rate of movement of bulk gas out is ________ the rate of movement of bulk gas into a liquid
equal to
True/False: Gases always travel down partial pressure gradients between biological compartments
True
True/False: Gases always travel down concentration gradients
False
The ______ O2 concentration determines the rate of most biological and chemical processes
absolute
Moles and mass are used to describe _____ gas concentration whereas % and mole fraction are used to describe ______ gas concentration
absolute, relative
According to Henry’s Law, at equilibrium, the solubility of a gas in a liquid is _______ the partial pressure of the gas above the liquid
directly proportional to
What is normal PaCO2 (arterial partial pressure of CO2)?
35 - 45 mmHg [ therefore 1.2 mM ]
Per Henry’s law, the value of CO2 in body is 1.2 mM compared to 6.9 uM in regular atmosphere (0.03%). Why?
Humans are CO2 making machines! :)
How much of inhaled O2 is consumed by the body?
4%
At equilibrium, what is the CO2 concentration in mM in the body? [at 37 C]
1.2 mM
What is the difference between PACO2 and PaCO2?
PACO2 is alveolar partial pressure of CO2; PaCO2 is arterial partial pressure of CO2
In normal lung function, what are the values for PACO2 and PaCO2, PvCO2?
for PA/Pa CO2 40 mmHg, they are roughly equal; for PvCO2 (venous) is 45 mmHg.
What is the Kacid value for H+?
794 nM
In normal human blood, what is the ratio of bicarbonate to CO2 [HCO3-]/[CO2]
20
What is the normal concentration of bicarbonate in blood?
24 mM
Is [H+] is completely controlled by which ratio.
PaCO2/HCO3-.
RATIO OF CO2 to bicarbonate is very important because it completely and totally dictates how acidic the blood will be.
If a patient has a PaCO2 of 30mmHg [lower than normal], is that patient acidemic or alkalemic? Why?
Do not known until you look at bicarb concentration
If the pt has a PaCO2 of 30 mmHg(low) and bicarb of 24mM (normal), what does this mean?
Ratio is lower than normal, which means H+ is lower than normal value of 40nM; which means pt is alkelemic [higher pH than 7.4]
If the pt has a PaCO2 of 30 mmHg (low) and a bicarb of 20 mM, which of the following are true?
a) their pH is inside the normal range
b) their [H+] <40 X 10^-9 M
c) their pH is >7.4
d) their H+ = 30 mM
e) their H+ = 30 M
Per [H+]=24XPaCO2/HCO3- Therefore [H+] = 30 nM So B is correct -log [30 X 10-9] = pH =-7.52, which is outside the normal range of 7.35-7.45 so A is incorrect. Their pH is over 7.4. Therefore B and C are correct
When a sample of whole blood is exposed to an increased PCO2, what will happen?
[HCO3-] will increase (as will H+ because equation shifts to right)
_________ states that if a dynamic equilibrium is disturbed by changing the conditions, the position of equilibrium moves to counteract the change
Le Chatelier’s principle
True/False: Clinically significant deviations from normal pH correspond to +/- 2 fold changes in [H+]
TRUE - only 2X
What happens to PaCO2 during a) hyperventilation, b) hypoventilation
a) will go down because blow off CO2; b) will go up because ventilation limited
What is the total concentration of the buffer system?
26 mM (1.2 CO2, 24 bicarb)
How does the bicarbonate system being open to the atmosphere help?
The open system allows for removal of CO2 which gives effective buffering even tho pKA = 6.1 is far from pH = 7.4
Why does the bicarbonate system not act as a buffer in response to changes in CO2
Because when CO2 increases, then bicarbonate increases. Can’t buffer itself!
WHen CO2 increases do to hypoventilation, what acts a buffer?
non-volatile buffers such as Hgb [absorbs some of the protons]
True/False: Changes in equilibrium are the same as buffering
FALSE FALSE FALSE FALSE
The bicarbonate system is important in buffering what two systems?
metabolic acid production (MAP), gastrointestinal acid production (GAP)
What are the two main processes that acidify the body?
Metabolism and endogenous acid production [MAP and GAP]
All _____ consumes bicarbonate whereas ______ creates bicarbonate [does not consume it]
endogenous acid production, metabolism
______ are the major source of metabolic acid production.
Proteins
Carbohydrates, lipids, and proteins are ________
net effect acidifying
Organic anions found in fruits and vegetables are ________
net alkanizing [K+A- instead of H+A-]
Complete oxidation of carbohydrates and lipids yields _____ whereas incomplete oxidation yields _______
CO2+H2O; organic acids (HA) [–> organic anion + H+ which is eventually consumed]
The pKas of organic acids such as lactic acid and pyruvic acid are all a) above normal pH b) equal to normal pH c) below normal pH
c (normal pH =7.4)
WHy do different diets produce different amounts of metabolic acids?
Non-industrialized tend to eat more fruit and veggies so lower rate; industrialized higher in meats and eggs so higher rate; hospitalized patients don’t eat so high
True/False: Daily CO2 production is over 100X greater than metabolic acid production (non-volatile)
True
________ is acid secreted by the gut into the blood for which ______ serves as a buffer
gastrointestinal acid production (GAP), bicarbonate system
True/False: Although the gut secretes both acids and bases into the blood, on average more base is secreted, so there is a net alkalizing effect
FALSE - acid, acidifying
Describe HCO3- and H+ secretion in the upper and lower gut.
In respond to a meal, cells of the upper gut secrete H+ into stomach and bicarb into blood; cells of lower gut secrete bicarb into lower gut lumen and H+ go into the blood.
The metabolic acid production is _____ of endogenous acid production while the acid secreted by the gut into the blood is ____ of endogenous acid production
2/3, 1/3
How do the lungs and kidney maintain body system pH?
use bicarb system and blowing off CO2; adding bicarbonate back to blood from kidneys
Does prolonged vomiting lead to acidosis or alkalosis? WHy?
Vomiting removes acid from stomach lumen; therefore gut cells must make more acid; this process causes bicarbonate to enter blood - therefore prolonged vomiting can lead to metabolic alkalosis
Does diarrhea lead to acidosis or alkalosis? Why?
Diarrhea removes bicarb in intestine; then intestinal cells must replace bicarb to lumen; causes protons to enter blood; can lead to metabolic acidosis
True/False: EAP causes acidemia in a normal patient
FALSE
Describe the process in which equilibrium is reeastblished after EAP putting acid [h+} into blood
HCO3- combines with H+ to buffer pH; CO2 levels transiently increase due to shift of equation to left; CO2 levels are returned to level via alveolar ventilation; HCO3- levels start to deplete so kidneys add more HCO3- to blood
What are two important buffers for ICF?
proteins, phosphates
What are the two sensors of CO2 levels and when are they activated?
central chemoreceptor in medulla (increased PaCO2 in medulla causes increase in ventilation) and peripheral chemoreceptor in carotid and aortic bodies (kick in when PaO2 falls below 60mmHg or when lactate threshold reached)
What two rates control arterial CO2?
metabolic production of CO2 and alveolar ventilation
True/False: Buildup of CO2 in the blood is due to an increase in metabolic CO2 production
FALSE - due to failure of some component of the respiratory system
True/False: Buildup of CO2 in the blood causes the PAO2 to fall (alveolar pressure O2)
True
True/False: PvCO2 refers to the blood that is entering the right side of the heart and then the the lungs via the pulmonary artery
TRUE - the venous refers to the composition of the systemic blood as it is reaching the right atrium and later the alveolus past the pulmonary artery
True/False: The terms hyper/hypo ventilation have nothing to do with the patient’s respiratory rate, depth or breathing effort
TRUE
Define the PaCO2 levels that make blood hypercapneic, eucapneic, and hypocapnic
Hypercapnia=> 45; eucapnia=35-45; hypocapneia<35.
Define hyperventilation and hypoventilation
They are defined in terms of PaCO2. Hyperventilation is PaCO2 <35. Hypoventilation is PaCO2 >45.
True/False: Hypercapnia is a sign of advanced organ system impairment
True
As PaCO2 increases, what happens to a) pH, b) alveolar ventilation, c) PAO2, d) PaO2
ALL FALLS DOWN [ unless pH compensated or inspired O2 is supplemented)
What is the only physiologic reason for elevated PaCO2?
the level of alveolar ventilation is inadequate for the amount of CO2 produced and delivered to the lungs
PACO2 normally equals PaCO2. What does this mean in terms of the PCO2 equation?
VCO2 (metabolic production of CO2, numerator) and alveolar production (denominator) must adjust accordingly
True/False: Alveolar ventilation rate is equal to the total ventilation rate
FALSE, total ventilate rate incorporates dead space as well. VA refers to ventilation rate of the ALIVE volume of the lung.
Total ventilation rate is equal to the product of ______ and ______
respiratory rate, tidal volume
The ______ is the volume of one breath [ under normal resting conditions]
tidal volume
___________ is the total amount of air breathed per minute that is exposed to “live” alveoli
alveolar ventilation
What three processes are required for gas exchange?
gas entering and leaving; diffusion of gas across capillary membrane; blood flow = perfusion
What is the difference between physiological dead space and anatomic dead space?
Anatomic dead space are airways that NEVER take place in gas exchanges because of normal anatomy. Physiological space include these areas plus dead alveoli that are not perfused
True/False: Anatomic dead space can be altered by broncodilation
TRUE - can be increased by dilating bronchi
What two factors will result in a patient becoming hypercapnic?
Inadequate total ventilation and increase in ventilated dead space
What would cause ventilation to be less than adequate?
anything that limits the rate or depth of breathing; examples: massive obesity, resp muscle weakness, severe pulmonary fibrosis, CNS depression
When the amount of ventilated dead space increases, the _______ requirement increases
minute ventilation
True/False: According to the PCO2 equation, the ONLY physiological reason for elevated PaCO2 is a level of alveolar ventilation inadequate for the amount of CO2 produced and delivered to the lungs
True
True/False: The body attempts to maintain steady state by holding PaCO2 and O2 constant
TRUE DAT
Atmosphere on earth contains _____ O2
21%
What is the atmospheric pressure of O2 (Po2 atm) at sea level and what happens to it when in a more elevated environment (such as in reno)?
159 mmHg, decreases
True/False: A terminal respiratory unit as defined by a physician is a single alveolus
FALSE - its the acinus - anatomic unit used by pathologist that includes 10-12 terminal respiratory units
True/False: In a terminal respiratory unit, PAO2 is equal to PaO2
FALSE NOT EQUAL. [they are equal in a single alveolus doe]
True/False: In a single alveolus, PACO2 = PaCO2
TRUE
True/False: PAO2 depends on the specific environmental conditions of the patient
TRUE such as the inspired air PIO2
True/False: The PAO2 is a predicted calculated value that is very close to what you would expect a patient to have if they were normal with NO GAS EXCHANGE DEFECT
TRUE
True/False: The PAO2 calculated from the alveolar gas exchange equation is equal to the measured PaO2 from an ABG in a healthy individual with no gas exchange problems
FALSE
True/False: PaO2 (arterial partial pressure) will always be less than PAO2 (alveolar partial pressure
TRUE DAT
What causes the A-a gradient to increase?
intrapulmonary gas exchange problems HOME SKILLET
What constitutes a normal P(A-a) O2 range
5-20mmHg
How would you calculate a normal PaO2 for someone’s age?
100-(0.4Xage)
How would you calculate a normal P(A-a)O2 difference for a patient’s age
[patient age/4]+4
What is the difference between hypoxic and hypoxemic?
Hypoxemia is defined as less than normal PaO2 or oxygen content in blood for person’s age. Hypoxia is defined as decreased oxygen supply to organs and tissues.
True/False: In order for a person to be classified as hypoxic, the pO2 in the blood must be low
FALSE - but hypoxia caused by hypoxemia is known as hypoxemic hypoxia[OMG YAY WTF KILL ME]
Hypoxia can result from all but which of the following:
a) cyanide toxicity
b) anemia
c) heart failure
d) shock
e) choking
e) all of the above
ALL
The NET gas transfer rate between alveolar air and pulmonary end capillary blood depends on what two steps?
rate of blood flow in; rate of gas diffusion across the barrier
What are the 5factors that affect gas diffusion rates across a barrier?
area, thickness, solubility, weight, partial pressure gradient
If the partial pressure gradient is the same, why does CO2 diffuse much faster than O2 across the alveolar membrane?
CO2 is 20X more soluble but weighs 1.37X more than O2 therefore diffuses 17X faster
________ is the time during which a RBC is transiting a capillary [involving alveolus] that enables gas exchange
capillary transit time
Capillary transit time is typically about ____. What can cause this time to be shorter
0.75 seconds, exercise
Under normal condtions, how long does it take an RBC to reach PO2 of 100% (load all the O2 it can get while transiting capillary)?
0.25 seconds
The extra 0.5 seconds between when the RBC is fully loaded (0.25 seconds) and the capillary transit time (0.75 seconds) is referred to as the _______
capillary reserve time [good for when exercising]
Under normal conditons, NET O2 transfer rate is limited by the rate of ______
perfusion
Which of the following would NOT lead to DIFFUSION limited NET o2 transfer?
a) emphysema
b) pulmonary fibrosis
c) high altitude
d) low physical activity
e) all of the above would lead to diffusion limited Net O2 transfer
D - severe exercise would cause this
True/False: Anything that decreases net O2 transfer will decrease PaO2 [and cause hypoxemia]
TRUE
How long does CO2 unloading from an RBC take on average?
0.45 seconds
True/False: PACO2 increases with exercise
FALSE. Body maintains homeostasis of CO2 by increasing ventilatory rate
True/False Under conditons where there is a gas exchange problem and diffusion across themembrane is slow, then exercise may lead to no unloading of CO2
TRUE - decreased transit time with exercise; depends on ability of person to increase ventilation to let go of CO2
True/False: Like O2, CO2 net gas transfer is perfusion limited under normal conditons
TRUE
What are the three challenges to the diffusion of gases between alveolus and blood?
severe exercise [shortens capillary transit time], pressure differences across membrane are lower [high altitude], membrane barrier thickening
What are three things that make diffusion go faster?
large diffusing area, high solubility of gas in barrier and blood, large differences in gas partial pressures
What are two things that make diffusion go slower?
thick barrier membrane, gases with higher mass
True/False: hemoglobin is a tetramer made up of two identical alpha and two identical beta chains
TRUE
Hemoglobin contains a hole in the center which changes size with ______
O2 binding
How many hemes are bound in the hydrophobic pocket of each Hgb subunit?
4
Where does iron bind to on the hemoglobin molecule?
Histidine side chain
True/False: Heme binds to Fe2+ and Fe3+ and then O2 can bind to either
FALSE - O2 can only bind Fe2+
What is cooperative O2 binding?
when o2 binds, it changes the conformation of the subunit, which transmits changes to other subunits and increases their affinity for o2
What is the O2 sensing mechanism of hemoglobin?
O2 binding to Fe2+ affects the degree to which Fe2+ is in the plane of the ring - this movement drags the His side chain with it and is reported to the rest of the molecule
What two components is the “heme” in hemoglobin composed of?
protoporphyrin IX and Fe2+
How does the red blood cell take care of hemoglobin?
it protects Hgb from proteases and protects it from the oxidizing environment of the blood [via enzymes that keep NADH and NADPH high]
How does hemoglobin take care of heme?
hydrophobic binding site on Hb keeps heme “soluble”
How does the hemoglobin-protoporphyin-IX take care of Fe2+?
it protects Fe2+ from oxidation to Fe3+ by O2 via specific coordination
How does Fe2+ take care of O2?
provides for reversible oxygen binding and transport
___ is the ultimate electron acceptor in the electron transport chain (if you don’t know this by now, you suck at everything)
O2
What are the two functional reasons for hemoglobin?
it protects Fe2+ from irreversible oxidation to Fe3+; it allows for reversible binding of O2 to Fe2+
True/False: Fe2+ is easily oxidized in air even if bound to heme (protoporphyrin-IX)
True
The _____ of deoxygenated hemoglobin is stabilized by 8 electrostatic interactions (salt bridges)
taut state
What happens to these salt bridges as O2 gets added to Hemoglobin
they break!! which is why cooperative O2 binding happens!!!
____ represents the percent saturation of hemoglobin with O2
SaO2
What is P50 equal to in terms of the Hb-O2 dissociation curve?
PaO2 when SaO2 is at 50%
True/False: A lower P50 would indicate looser binding
False, would indicate tighter binding. Means hemoglobin is 50% saturated at smaller PaO2
Hemoglobin dumps about ____ of O2 from when moving from lungs to tissue. This number increases to _____ via cooperative O2 binding when hypoxic tissue is involved.
18%, 63%
What 3 factors change the Hb-O2 dissociation curve and how?
pH, CO2, temperature - shift curve to right without changing the shape
What causes an increase in P50 (less binding affinity)
increased temperature, increased acid [h+], increased PaCO2 [hot, sweating, and gasping]
Why would you want to decrease the binding affinity of O2 for Hb?
if you need more free O2 for use in mitochondrial electron transport chain [such as during exercise]
How does H+ weaken O2 binding to Hb?
Low pH favors the taut state because high proton concentration keeps a His protonated which stabilizes a salt bridge - this salt bridge has to be broken to favor O2 binding - this requires energy so O2 binding is weaker
True/False: When tissues are more acidic, there is a higher metabolic rate, so need more O2
True [ think hypoxic tissues during exercise ]
The Bohr effect ensures that there is additional deliver of O2 to hypoxic tissues during exercise due to _____ and _____ at these tissues
lower pH, higher CO2
True/False: CO2 binds to Hb active site
FALSE
How does increased CO2 weaken O2 binding to Hb?
CO2 stabilizes deoxyHb by reacting to form carbamoylated Hb. Carbamate participates in the salt bridge so it is strengthened which means O2 binding is weakened.
True/False: More “free” O2 is needed when tissues are producing a lot of CO2
yes because high metabolic activitiy
What is the difference between the Bohr effect and Haldane effect?
Bohr: CO2/H+ weaken O2 binding to Hb; Haldane: O2 weakens CO2/H+ binding to Hb [ shifts reactions in opposite directions ]
O2 handling is coupled to ______
acid handling. Cellular metabolism produces acids and requires O2.
Hb-O2 complex combines with H+ to produce what two components?
H+Hb complex and O2
HbO2 complex combined with CO2 to produce what three components?
Hb-COO-, H+, O2
What happens with increases CO2 and H+?
The reactions shift to produce more O2 which means that HbO2 complex weakens and H+Hb and Hb-COO- complexes are produced [ CO2 and H+ lead to weaker binding of Hb with O2]
What happens with increases in O2?
The reactions shift to produce more H+ and CO2 which weakens H+Hb and Hb-COO- complexes to form HbO2 complex [ O2 leads to weaker binding of Hb to CO2 or H+]
How does 2,3 bisphosphoglycerate weaken O2 binding to Hb?
2,3 BPG binds to hole in Hb and stabilizes deoxy-hb. O2 doesn’t like BPG and doesn’t bind. RIght-shifted curve.
What happens to concentrations of hemoglobin, BPG, and the # of RBCs at high altitude?
they all increase. More hemoglobin means improved O2 transport. More BPG means more O2 dumped at tissues.
True/False: Fetal hemoglobin (HbF) has higher O2 affinity than HbA (adult Hgb)
True
Does the fetus Hgb bind 2,3-BPG as readily as adult hemoglobin? What are the implications of this?
It does not. This allows fetus to win O2 fight with mother because has higher affinity for O2 [BPG not bound so no weakening]. LEFT SHIFT OF CURVE.
CO2 in the blood is 70% ______, 20% _____ and 10% _____
bicarbonate, carbamino form, dissolved CO2
True/False: Most of the O2 in blood is bound to Hb while a small amount is dissolved O2
TRUE
What are the three fates of CO2 [produced by tissues] after it diffuses into the blood?
1) it can remain in plasma where it reacts with H2O to produce H+ and bicarb (HCO3-) [no carbonic anhydrase so slow AF]; 2) CO2 can diffuse into RBC and rapidly equilibrate to bicarb and H+ in presence of CA]; 3) CO2 can diffuse into RBC and react with N-terminus of HbO2, promoting release of O2 and H+
The second path CO2 can take is it diffuses into the RBC where carbonic anhydrase reaction produces bicarb and H+. What are the consequences of this reaction?
H+’s are buffered via reaction with HbO2 which weakens O2 binding and causes O2 to move down its gradient [free]. Bicarb exits RBC and Cl- comes into RBC, this leaves room in RBC for more CO2 to dissociate to H+ and HCO3-
The third path is that CO2 can diffuse into RBC and react with the N-terminus of HbO2 which releases O2 and H+. What are the consequences of this?
H+ generated which also binds HbO2 and weakens O2 binding. O2 directly generated by this reaction also moves down gradient.
True/False: Metabolic acids (H+) also bind to HbO2 and promote more O2 dissociation.
True
CO2 diffusing into RBC generates ____ which are consumed by reacting with ____ to make ____ and ____
CO2, H+, HbO2, HbH+ and O2
Both H+ and CO2 are transported to the lung by ______ in the form of _______ and ____
deoxy-Hb, carbaminoHb and HbH+
When deoxygenated blood enters the pulmonary capillary and encounters blood with increased PO2, what two fates does the RBC undergo?
The O2 binding to hemoglobin weakens the HbH+ bond and H+ is generated; O2 binding to carbaminoHb weakens CO2 binding (Haldane)
When O2 binding to Hb weakens HbH+ binding, producing protons in the pulmonary capillary, what happens to the protons?
They are buffered by the bicarbonate system –> produces CO2 which leaves RBC down its pressure gradient
The chloride shift is the exchange of _____ and ____ across the membrane of RBCs
HCO3- and Cl-
When O2 binding to carbaminoHb weakens CO2 binding in the pulmonary capillary, what happens to the CO2 that is produced?
Co2 that is generated leaves down its gradient.
Either way, RBCs entering the pulmonary capillary lead to generation of ___
HbO2
____ is a compound produced by tobacco and car and furnace exhaust which competes with O2 at the heme binding site
CO
True/False: At CO concentrations as low as 0.02% in inspired air, headache and nausea result with unconsciousness following at 0.1% concentration
True
In heavy smokers, up to ___ of oxygen-active sites can be blocked by CO. Why?
20%; CO binds 200X more tightly to heme than O2.
True/False: At high [CO] patient can be hypoxic while maintaining a normal PaO2
TRUE. O2 partial pressure doesn’t change but CO decreasing MAXIMAL O2 binding capacity.
True/False: COHb levels can be estimated reliably by measuring [CO] in breath
True
Describe the effects of methemoglobinemia on the O2 binding curve and oxygen delivery.
Methemoglobinemia is an altered state of Hgb in which the ferrous (2+) form of heme is oxidized to the ferric form (3+) - so heme unable to bind oxygen. The remaining heme within the tetramer will therefore bind O2 more tightly –> left shift of dissociation curve and reduced oxygen delivery at tissue level
True/False: Calculated SaO2 is only reliable if nothing but O2 is binding to the hemoglobin
TRUE
True/False: SaO2 can be directly measured in a co-oximeter and all pulse-ox machines
FALSE ONLY SOME PULSE OX
What is the difference between pulse oximetry and SaO2 co-oximeter?
pulse oximetry measures SpO2 - may or may not distinguish between CO-Hb, Met-Hb, and O2-Hb [so may be different value than SaO2]
What is the total O2 content (CaO2) equal to? Which values are reported by PaO2?
O2 (diss) + O2 (Hb bound). Only O2 dissolved gas is reported in PaO2.
True/False: O2 molecules bound to Hb still exert pressure
FALSE - no longer do
What is the difference between paO2 and CaO2?
PaO2 represents the dissolved O2 content and is determined by alveolar O2 and lung architecture (Hb has no influence). CaO2 includes all the O2 present, dissolved and Hb bound and depends on Hb concentration; also depends upon SaO2.
True/False: PaO2 is a function of hemoglobin content
FALSE - only a function of the alveolar PO2 and the lung architecture
IF a patient has a severe hemolytic reaction that suddenly cuts her Hgb in half, but no lung disease occurs, what will happen to her PaO2, SaO2, and CaO2?
PaO2 will be unchanged because no lung disease therefore no effect on the partial pressure of O2.
SaO2 will be unchanged because not affecting hemoglobin binding to O2 just affecting overall Hgb concentration.
CaO2 will be reduced per CaO2=Hb1.34SaO2 - CaO2 is dependent on the Hb concentration.
_____ is impaired oxygen delivery to tissues whereas ______ is low CaO2 in blood caused by reduction in PaO2, SaO2 or [Hb]
hypoxia, hypoxemia
What is the difference between SaO2 and CaO2?
SaO2 is the % of available hemoglobin in the arterial blood that is bound to O2; CaO2 is the total oxygen content in the arterial blood [dissolved and bound to Hgb]
V/Q mismatch, hypoventilation, decreased PiO2 would lead to a decrease in
a) PaO2
b) SaO2
c) Hb
a
CO poisoning, methemoglobinemia, acidemia would lead to a decrease in
a) PaO2
b) SaO2
c) Hb
b
Reduced CO would lead directly to reduced _____
O2 delivery to the tissues
What two conditions would cause decreased tissue O2 uptake?
poisoning of the mitochondria (cyanide) and left-shifted O2 binding curve (alkalemia, CO poisoning)
If given values of PaO2, SaO2, Hb for two patients, how would one conclude which was more hypoxemic?
Do the CaO2 equation = Hb1.34SaO2
True/False: More O2 is dumped to the tissue by Hb tetramer than monomer
True
True False: When there is an extrapulmonary issue, PACO2 is always raised
TRUE DAT. there is no intrinsic problem to lung and its alveolar units; some extrapulm factor is limiting VA
What are the two main categories of hypoxemia?
not enough O2 getting into alveoli and not enough O2 transferred into the capillary blood
True/False: Pure hypoventilation and decreased PIO2 cause hypoxemia because not enough O2 is getting to alveoli
True
What three causes of hypoxemia fall under the “not enough O2 is transferred into the capillary blood” category
V/Q mismatch, right to left shunting, diffusion defects [ also architecture of the lungs]
True/False: Anything that limits the rate or depth of breathing can lead to hypoventilation
TRUE
In cases of hypoventilation, how can hypoxemia and hypercapnia be corrected?
Increase FiO2 and mechanically ventilate the patient
True/False: In pure hypoventilation, the A-a difference is large and abnormal
False - it is small and normal. The decrease in PAO2 stimulates decrease in PaO2 and therefore the A-a difference is normal. [PaCO2 is elevated doe]
What decreases PIO2 and what would this lead to [think of equation]?
Low PIO2 can be caused by high altitude or respirator delivering low FIO2. PAO2 decreases, which leads to low PaO2 –> hypoxemia
________ is any fraction of the venous blood that does not get fully oxygenated. What are two normal reasons for this?
wasted blood; anatomic shunt; low regional V/Q ratios
If measuring PaO2 and PAO2 in a normal human body, where would you find that PA=PaO2
when measuring the end pulmonary capillary blood (basically at level of single alveolus)
What is the main reason for a PA-aO2 difference in normal individuals?
PAO2>PaO2 if there is any anatomic shunt [it is normal to have a shunt]. Also, if measure systemic arterial blood, will have lower PaO2 value than PAO2
In the bronchial circulation, a normal anatomic shunt is a portion of the venous blood from the bronchial circulation which is destined for the ______ draining into the ______ instead
conducting zone, pulmonary vein
In the coronary circulation, a normal anatomic shunt is a portion of the coronary circulation’s venous blood draining through the ______ into the _____
thesbian veins, left ventricle
Normal anatomic shunts represents ___ of the cardiac output
2%
What are two congenital abnormalities that raise the A-a gradient above the normal expected values?
inter-cardiac shunt (such as tetraology offallot: VSD, pulmonary artery stenosis) and intrapulmonary fistulas (direct communication between branch of pulm artery and pulm vein)
________ is the mixing of unoxygenated blood with oxygenated blood
venous admixture
True/False: Normally, alveolar ventilation is about the same as the pulmonary blood flow rate
True
Gas exchange depends critically on the proper matching of ________ and _______
ventilation, perfusion
When V/Q = 0, what does this mean?
ventilation is totally absent; shunt [blood coming out is the same composition as venous blood because no ventilation]
When V/Q = infinity; what does this mean?
dead space, perfusion is totally absent
When V/Q is very high, what is the composition of the gases in the blood?
there is no blood flow from the unit, so the gases leaving the unit are the same as atmosphere - PO2 is high at 150 and PCO2 is low at atm
Generally, in the lung V/Q ratios approach 1. What is the main difference between the apex and the base?
GRAVITY [low at base, higher at apex]
Physiological dead spaces and shunts are normal until they reach abnormal levels. In disease states, what happens when alveolar spaces fill with fluid [pneumonia, drowning]?
a portion of the cardiac output goes through regular pulmonary vasculature but does not come into contact with alveolar air due to fluid NOT OXYGENATED
What two normal effects cause the normal A-a difference of 10-15?
gravitational effects on V/Q, anatomic shunting (2-5% of CO)
True/False: At sea level, none of A-a difference is caused by a diffusion limitation (decreased rate of diffusion across the alveolar-capillary barrier), except for during exercise
FALSE - none of the A-a difference caused by this even during exercise
In an unhealthy pt, an elevated P(A-a)O2 difference is due to a _______
V/Q mismatch among different alveoli
True/False: If the hemoglobin content is the same for mixed samples, then CaO2 will be proportional to SaO2
TRUE
Alveolus 1 has a V/Q of 1.3 [PAO2 of 116] and Alveolus 2 has a V/Q of 0.3 [PAO2 of 66] due to constriction of the air vessels. Is the average SaO2 leaving the unit less, equal or greater than the normal value of 97%
It is less because the hypoxemic alveolus that is not getting well ventilated drags the average SaO2 down. The hyperoxemic alveolus that is super well-ventilated cannot bring the SaO2 up much because hemoglobin can has a point of complete saturation, so extra oxygen only helps to a degree.
TrueFalse: When you mixi two equal volumes of blood with different PO2, the resultant PO2 is equal to the mean of the two PO2s
FALSE - equal to the mean of the two CaO2 (which approximates the mean of the two SaO2)
True/False: Due to the flat shape of the oxygen binding curve, the resulting PO2 after mixing is lower than the mean PO2
TRUE
When you mix unequal volumes of blood with different PO2, the PO2 is equal to the _______
flow-weighted average of SaO2s
Can supplemental O2 rescue effects of perfused by not ventilated region (shunt)? [V/Q = 0]
NO - resulting arterial hypoxemia is refractory to supplemental inspired oxygen
What is a shunt?
AN AREA OF THE LUNG THAT IS PERFUSED BUT NOT VENTILATED
Describe the values of PaCO2, A-a gradient and response to supplemental O2 that would lead to suspicion of a shunt
the A-a gradient is large, and there is no response to supplemental O2. The PaCO2 would be normal UNLESS pt is hypoventilating then PaCO2 would be elevated
Can supplemental O2 help V/Q mismatch?
YAAAAAAS
Describe the changes in PAO2 and PACO2 with a) VQ = 1; b) V/Q >1; c) V/Q<1
If V/Q=1 PaO2 will be about 100 and PCO2 will be 40; if V/Q >1, PAO2 will be higher and PACO2 will be lower; if V/Q <1, PAO2 will be lower and PACO2 will be higher
True/FalseWhen there’s V/Q mismatching between two alveoli, the hypoxemic one ALWAYS wins.
True
True/False: V/Q mismatching is the major clinical reason for hypoxemia
True
True/False: V/Q mismatching is the MOST important cause of gas exchange abnormalities in most lung diseases
TRUE
Although V/Q mismatch can influence PaCO2, this effect is often overcome by an increase in _______
minute ventilation
When would PaCO2 be affected by degrees of V/Q mismatch that routinely lead to hypoxemia?
WHen there’s insufficient alveolar ventilation
True/False: P(A-a)O2 is normal at rest but may be elevated during exercise
true
______ is the collapse or closure of a lung resulting in reduced or absent gas exchange
atelectasis
What are the effects of V/Q by alveolar filling or atelectasis? These conditions can be caused by pulmonary edema or severe pneumonia.
shunt - V/Q=0
Airway obstruction leads to a ____ in V/Q. This can be caused by asthma or chronic bronchitis
decrease
Perfusion blockage and loss of lung parenchyma leads to a _____ in V/Q. These can be caused by an embolism or loss of lung parencyhma
Increase
