Hemoglobin and Blood Gas Transport Flashcards
Hb is a (blank) and is mostly helical –globin fold
tetramer (4 non-covalently bound subunits)
What does this hole in the center –size changes with O2 binding a2b2 Two identical alpha chains Two identical beta chains Extensive interactions between ab pairs
hemoglobin
For hemoglobin:
4 hemes tightly bound in hydrophobic pocket of each subunit
Heme is (blank)
Has (blank X 3) side chains –help keep heme positioned in the binding pocket
planar
proprionyl, methyl and vinyl side chains
Iron binds to (blank) side chain on Hb
His
Heme binds to Fe+2 and Fe+3 but O2 can only bind to (blank).
O2 binding exhibits (blank) binding
Fe+2
cooperativity of O2 binding
O2 binding changes the (blank) structure of hemoglobin.
Basis of the cooperativity mechanism
tertiary and quaternary
Each Hb subunit binds (blank) to one heme
non-covalently
(blank) takes care of hemoglobin by protecting it from (blank) and (blank) via enzymes to keep NADH and NADPH levels high.
RBC
Proteases and Oxidization (via plasma environ.)
Hemoglobin takes care of heme via hydrophobic binding site on hemoglobin keeps heme (blank)
soluble
Fe+2 is coordinated to 4 pyrrole nitrogens of (blank)
protoporphyrin IX
How does Hb-protoporphyrin-IX take care of Fe+2?
protects iron from oxidation
positions iron to favorable O2 binding
provides O2 sensing mechanism
What is this?
O2 binding to Fe+2 affects the degree to which Fe+2 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
O2 sensing mechanism
What does Fe2+ do for O2?
provides for reversible oxygen binding and transport
(blank) is the ultimate electron acceptor in electron transport chain.
O2
What are the 2 functional reasons for Hb?
1) protection for Fe2+ from irreversible oxidation to Fe3+
2) Allows for reversible binding of O2 to Fe2+
Fe2+ is easily (blank) in air even if bound to protoporphyrin IX. If this occurs, O2 will become a (blank)
oxidized
superoxide anion radical
Fe2+ is protected from oxidation when bound to (blank)
Hb-protoporphyrin-IX
O2 reduction is (blank), reversible O2 binding is (blank)
bad
good
What state is the Hemoglobin in?
Taut state = T state
8 electrostatic interactions (salt bridges) stabilize the T state
deoxygenated Hb
When you bind the first O2 to deoxy Hb, what happens?
change structure-> break salt links-> change conformation in adjacent subunits
When you bind the first O2 to deoxy Hb what do you need to break your salt links and is the effective affinity for the FIRST O2 strong or weak? What allows for cooperative binding? Do the bonds become weaker or tighter as you continue to bind O2 to Hb?
energy
weak
breaking salt links
tighter (stronger)
On a cooperative Hb- O2 binding curve,what is P50?
The lower the P50, the (blank) the binding.
What is the P50 of HbA?
PaO2 when SaO2 (%of Hb bound to O2) is at 50%
tighter
27mm Hg
On the cooperative Hb- O2 binding curve Sigmoidal shape of the curve allows for efficient (blank) to hypoxic tissues. What percent of potential O2 binding sites have dumped their O2 to tissues?
O2 dumping
18%
~63 % potential O2 binding sites have (blank)
contributed to O2 transport
What factors shift the Hb-O2 dissociation curve to the right WITHOUT changing the shape?
pH, CO2, Temperature, BPG too
If you have an increase in P50 you have a weaker or tighter bond of O2 to Hb?
weaker!
If you have an increase in P50, what can be the cause? What shift will take place on the Hb-O2 dissociation curve?
increased temp, increased acid [H+], increased PaCO2
Easy to remember = HOT, SWEATING, and GASPING. Think muscle.
Right shift
How does increased [H+] weaken O2 binding to Hb? (part of bohr effect)
Low pH favors the T state due to increased [H+] which stabilizes salt bridges. remember you need these broken to favor O2 binding
When you have high [H+], what happens to the binding affinity of O2 to hemoglobin?
H and O2 bind to hemoglobin but dont like binding at the same time. H+ binds in place of O2 so the hemoglobin drops O2 for H+. This is important because this is exactly what you need when you have an acidic environment, you need more oxygen leaving hemoglobin and entering into your tissues!!!
When you have higher metabolic rate in tissues what do you need?
you need hemoglobin to pick up the acid and drop the oxygen
Normal shape of the curve allows steep increase in O2 dumping to hypoxic tissues during (blank). Additional delivery due to lower pH and higher CO2 at the hypoxic tissues
exercise
How does an increase in CO2 weaken O2 binding to Hb?
Co2 stabilizes deoxy-Hb by reacting w/ amino group and creating carbamoulated-Hb which makes salt bridge. We want this! if you have more CO2 in your blood you dont want o2 binding to hemoglobin you want it roaming free in your tissues
What is the Bohr effect?
What is the Haldane effect?
Bohr-CO2/H+ weaken O2 binding to Hb
Haldane-O2 weakens CO2/H+ binding to Hb
O2 handling is coupled to (blank) handling
acid
How does BPG (2,3 bisphosphoglycerate AKA DPG) weaken O2 binding to Hb?
Binds in hole of Hb which stabilizes deoxyHb. BPG and O2 dont like to bind together so you have one or the other binded to Hb. When you have chronic hypoxia you will have an increase in BPG
What does BPG do to the cooperative Hb-O2 binding curve?
right shift
BPG is always around but can be increased under certain conditions. What is an example of one of these?
high altitudes
What does high altitude do to your body?
Increase # of RBC
Increase [Hb]
increase [BPG]
adaptation to high altitude improved both amount of (blank) transported (more Hb) and efficiency of o2 dumping at tissues which will shift the curve to the (blank)
O2
right
What are the three predominant pathways of carbohydrate metabolism in the RBC?
glycolysis (creates ATP)
2,3 BPG metabolism (unique to RBC, ATP investor)
Pentose Phosphate Shunt (creates NADPH for the reduction of methemoglobin)
Which has higher O2 affinity, HbF or HbA?
HbF!!!!
HbF (fetal Hb) α2γ2
Binds (blank) much less avidly than HbA (adult Hb).This is important becaues….?
BPG
Fetus does not experience BPG-induced weakening of O2 binding
Fetus wins O2 fight with mother because has higher affinity for O2, this will create what kind of shift on the Hb-O2 cooperativity curve?
Left shift
CO2 in blood is (blank)% dissolved CO2, (blank)% bicarbonate, and (blank)% carbamino form.
10%
70%
20%
In the capillary what is happening with oxygen and hemoglobin?
you have high alveolos oxygen which pushes oxygen into blood and you have high SaO2 (oxygen bound hemoglobin) and Co2 is ventilated and removed
In the arterial blood, going to the tissues what is happening with oxygen and hemoglobin?
Most O2 is bound to hemoglobin in blood
small amount of o2 is dissolved in blood
The conditions of the tissues promote the release of (balnk) from Hb. How?
o2
partial pressure gradients allow for unloading of o2 into tissues and free o2 that is dissolved in blood diffuses into tissues and is used in the ETC
The tissues produce CO2, what happens to this CO2?
1) can remain in plasma and react with H20 to become H and bicab in presence of Carbonic anydrase
2) Co2 can diffuse into RBC and equilibrate to bicarb and H in presence of carbonic anydrase
3) CO2 can diffuse into RBC and react with N-terminus of HbO2, promoting relase of O2 and H (bohr effect)
If Co2 diffuses into RBCs and equilibrates to bicarb and H+ in the presence of carbonic anydrase, what happens to the new H+’s?
the H+s generated are buffered by reacting with HbO2 which weakens the O2 binding (bohr effect) and O2 moves down its partial pressure gradient. HCO3- is left behind, goes out of the RBC and Cl- comes in, which leaves room in the RBC for move CO2 to dissociate to H+ and HCO3-
If CO2 diffuses into RBCs and reacts with the N-terminus of HbO2 to promote the release of O2 and H+ (Bohr effect) what will happen to the the H+?
the H+ generated will bind to HbO2 which weakens O2 binding (bohr effect) and O2 moves own its partial gradient. O2 directly generated by this will passively diffuse across the partial pressure gradient
The CO2 diffusing into RBC generates H+, which are consumed by the reaction with (blank) which makes (blank) and (blank)
HbO2 which makes HbH++ and O2
What happens to H+, CO2 and O2 in the transit in venous blood to the lung?
Both H+ and CO2 are transported to lung by deoxy-Hb in the form of carbaminoHb and HbH+. As H+ is increases some gets consumed by HCO3 to make CO2. some of H+ gets buffered by nonvolatile buffers.
What happens when blood enters the pulmonary capillary?
O2 diffuses into RBC, PO2 increases in capillary blood.
What are the 2 paths that O2 binding can take in the pulmonary capillary?
Path 1: O2 binding to Hb weakens H+ binding to Hb (Haldane), H+ generated
Path 2: O2 binding to carbamino-Hb weakens CO2 binding (Haldane)
What are the consequences of path 1 and 2 of O2 binding in the pulmonary capillary?
Path 1 generates protons which are buffered by the bicarbonate system making CO2 which tends to leave the RBC down its pressure gradient
Buffering requires that bicarb is consumed so it backfills from the plasma by reversal of the chloride shift
Path 2 also buffers the protons generated in path 1 and CO2 is generated to leave down its gradient
Both path 1 and 2 generate HbO2
What compounds compete with O2 at the heme binding site? (not allosteric effectos)
CO and other toxic molecules
(blank) poisoning is an important reason for emergency department (ED) visits during winter months
Headache
Carbon monoxide (CO)
What does this describe:
Heavy smokers - up to 20% of the oxygen-active sites can be blocked by this.
This binds ~200 times more tightly to heme than O2
This decreases maximal O2 binding capacity
At high concentrations of this, patients can become hypoxic while maintaining a normal PaO2
Carbon monoxide
Methemoglobinemia is an altered state of hemoglobin which makes the heme moiety unable to bind oxygen. In addition, the
remaining monomers of ferrous heme within a hemoglobin tetramer bind their oxygen more tightly causing a (blank) shift of the oxygen dissociation curve and reduced oxygen delivery at the tissue level.
left shift
Normally, methemoglobinemia is kept low by anti-oxidant enzymes. Therefore when will you get an increase in metHB?
if you have an enzyme insufficiency
SaO2 (calc) is only reliable if (blank) is binding to the Hb
nothing but O2
SaO2 can be directly (Blank) in a co-oximeter and some pulse-ox machines.
Co-oximeter measures all the Hb-related values ([Hb], metHb, CO-Hb, SaO2, and calculates CaO2)
measured
What does Pulse Oximetry do?
measures SpO2; Pulse oximetry may or may not distinguish between CO-Hb, met-Hb, and O2-Hb
Are these measured or calculated:
SaO2?
O2?
measured
calculated
What is the equation for total O2 content?
How much is dissolved and how much is bound by Hb?
Which value is reported by PaO2?
CaO2= O2dissolved + O2 (Hb bound)
1.5 % dissolved gas
98.5 % bound to Hb
the dissolved amount
PO2 is the partial pressure of O2 molecules (blank).
Once O2 molecules bind to Hb they (blank) exert pressure!!
dissolved in the plasma.
no longer
PO2 (blank) measure the O2 in the blood that is bound to Hb!
does NOT
What is the CaO2 equation (remember you have to calculate CaO2!)?
CaO2= ([Hb] X 1.34 ml O2 X SaO2)/ (100)
SaO2 is reported as a % but in this equation you must divide it by 100 to get the calculation to work.
What does this:
Represents the dissolved O2 content
Determined by alveolar O2 and lung architecture (has nothing to do with Hb)
PaO2
What does this:
Includes all the O2 present, dissolved + Hb-bound
Depends upon Hb concentration
Depends upon the SaO2
CaO2
When calculating CaO2. what do you ignore? what is the normal value? is it calculated?
you ignore dissolved O2
normal= 20
CaO2 is calculated
What is the most non specific finding and the least helpful?
PaO2
Can a patient have a normal PaO2 and be starved of O2?
yes
To know the CaO2, you need the (blank) and (blank).
SaO2 and Hb
(blank) is impaired O2 delivery to the tissues or low levels of PaO2 expected for age
hypoxia
How can you get hypoxemia?
low CaO2 in blood caused by reduction in PaO2, SaO2, or [Hb]
What are these causes of:
Respiratory causes
V/Q = 0, left to right shunt of pulmonary blood
V/Q
Reduced PaO2
What are the causes of this:
all of the same causes of reduced PaO2 plus CO poisoning, methemoglobinemia, and acidemia
Reduced SaO2
Is SaO2 and PaO2 effected by concentration of hemoglobin?
no
When will you get reduced [Hb]?
anemia (lower than normal number of RBC)
What are the causes of Hypoxia?
1) hypoxemia
2) Reduced O2 delivery to the tissues
3) decreased tissue O2 uptake
When you have reduced cardiac output what will happen to your O2 delivery to tissues?
it will be reduced
Poisoning of mitochondria (cyanide), and a left shift of the O2 binding curve (alkalemia, CO poisoning) can cause what?
a decrease tissue O2 uptake
