O2 sensing mechanism of Hb
O2 binds to Fe2+ and affects the degree to which Fe2+ is in the plane of the ring. The movement drags the His side chain with it and Hb can sense this shift.
How do RBCs take care of Hb?
- protects it from proteases
2. protects it from oxidizing environment of plasma
How does Hb take care of heme?
Hb has hydrophobic binding sites that keep heme soluble.
How does Hb-protoporphyrin-IX take care of Fe2+?
Protects fe2+ from oxidation to fe3+
How does Fe2+ take care of O2?
Provides for reversible binding of O2 and transport
2 functional reasons for Hb
- prevents Fe2+ from irreversible oxidation to Fe3+
2. allows for reversible binding of O2 to Fe2+
As you add O2 to Hb, it becomes easier to bind the O2. Why is this so?
Some salt links have already been broken!
How do you find SaO2?
(HbO2/Hb+HbO2) * 100
What does a lower P50 indicate?
Tighter binding affinity of O2 for Hb
Normal P50 for HbA
27mmHg
From lungs to tissues, about what percent of O2 binding sites have dumped their O2?
18%
If there is hypoxia, RBCs can dump up to (blank)% of their oxygen to the tissues that need it most.
63%
Things that can shift the Hb-O2 dissociation curve to the right?
pH, CO2, temperature, BPG
Things that cause weaker binding of O2 to Hb (right shift)
Hot, sweating, gasping
- increased temp
- increased [H+], lower pH
- increased PaCO2
How does increased H+ weaken O2 binding?
H+ stabilizes the salt bridges that need to be broken for O2 to bind!
H+ and O2 do not like to bind at the same time. So what does decreased pH (more H+) cause?
Decreasing pH forces Hb to dump some O2 to tissues. This is helpful under acidic conditions, because tissues need more oxygen!
How does CO2 weaken O2 binding to Hb?
Favors formation of carbamate, which stabilizes salt bridges that must be broken for O2 to bind.
So, what are the two things that do not like to bind with O2?
H+ and CO2
(Bohr/Haldane) says that CO2/H+ weakens O2 binding to Hb. (Bohr/Haldane) says O2 weakens CO2/H+ binding to Hb.
Bohr; Haldane
How does BPG weaken O2 binding to Hb?
Binds in the central hole in Hb. O2 and BPG do not like to bind to Hb at the same time. So, this causes chronic hypoxia.
What three things increase at high altitude?
- number of RBCs
- [Hb]
- [BPG]
What are the three pathways that describe carbohydrate metabolism in the RBC?
- Glycolysis
- 2,3-BPG metabolism
- Pentose phosphate shunt
Fetal hemoglobin has a (blank) affinity for oxygen, and causes a (blank) shift in the O2 curve.
Higher; left
Main compound that we talked about that can compete with O2 at heme binding site?
CO – CO binds 200 times more tightly to heme than O2.
CO decreases maximal O2 binding capacity, so at high [CO] patient can be hypoxic while maintaining a normal (blank)
PaO2
An altered state of hemoglobin in which the ferrous (2+) form of heme
is oxidized to the ferric form (3+) thus making the heme moiety unable to bind oxygen
Methemoglobin
What does a pulse ox measure?
SaO2
What is the equation for total O2 content? What variable in the eq is reported by PaO2 and which is not?
CaO2 = Hb · 1.34 · SaO2/100
Total O2 content = CaO2 = O2(dissolved) + O2(bound to Hb)
O2 dissolved is reported by PaO2, but O2(bound to Hb) is not!
Is there more O2 bound to Hb or freely dissolved?
Much more bound to Hb. Ex: 20ml bound, 0.48ml free
So what is the main difference between PaO2 and CaO2?
PaO2 represents only dissolved O2 content, and does not account for O2 bound to Hb. CaO2 includes all O2 present!
What is a normal CaO2?
20!
Which value is most useful? PaO2 or CaO2?
CaO2! A patient can have a normal PaO2 and be starved of O2!
Impaired O2 delivery to the tissues
Hypoxia
Low CaO2 (oxygen content) caused by reduction in PaO2, SaO2, or [Hb]
Hypoxemia
3 causes of hypoxia
- Hypoxemia: reduced PaO2, SaO2, or [Hb]
- Reduced O2 delivery to the tissues
- Decreased tissue O2 uptake
PCO2 equation
PaCO2 = VCO2 * 0.863 / VE – VD
Henderson-Hasselbalch equation
pH = 6.1 + log [HCO3-]/0.03*PaCO2
Alveolar gas equation
PAO2 = PIO2 – 1.2(PaCO2)
A-a difference equation
P(A-a)O2 = PAO2 – PaO2
Oxygen content equation (CaO2)
CaO2 = Hb · 1.34 · SaO2