Intro Flashcards
Respiratory system
Body part and anatomical designs that enable us to move air and exchange vital gases
In equilibrium gases move down pressure gradient
There is no active pump to get oxygen into the blood
Similarly, no pump to get CO2 out of the blood
Movement occurs by diffusion
Partial pressure
Pressure a single component gas would exert if it were removed from the gas mixture and placed in an equivalent volume
Law of partial pressure (Dalton’s law)
total pressure in a system is the sum total of all the partial pressures of the (non-reacting) gases
Atmospheric pressure
“Room air” = air exposed to atmosphere pressure (Patm)
Patm also called barometric pressure
Inspired air, dry
160 mmHg
Inspired air, saturated with water vapour
150 mmHg
Alveolar gas
100 mmHg
Arterial blood
95 mmHg
Tissues, interstitium
40 mmHg
Mitochondria
4-10 mmHg
Alveolar gas equation
PAO2 = [(Patm – PH20) x FiO2] – (PaCO2/RQ)
Respiratory quotient
Ratio of molecules of CO2 produced for molecules of )2 consumed
Oxygen carriage in blood
- solubility
- dissolved O2 content
Oxygen is very soluble
Dissolved O2 content = 0.003 mLO2/dl/mmHg x PO2
So even with a PaO2 ~100 mmHg, the amount of oxygen dissolved in blood is small (~15 mL/min in entire blood pool)
Oxygen consumption(VO2) of the body, AT REST, is around 250 mL / min
Henry’s Law
A gas dissolves in a liquid in direct proportion to its partial pressure and solubility.
Haemoglobin O2 saturation
Hemoglobin subunits can be in a T (taut) or R (relaxed) state. T state subunits are NOT able to bind O2. R state hemoglobin are able to bind O2.
Saturated (oxy-Hb)
Range: 0-100%
Haemoglobin saturation measurement
A probe is placed on the finger, toe, ear lobe or nose. Two light-emitting diodes produce beams at red and infrared frequencies (660 nm and 940 nm, respectively). There is a photo detector on the other side. The diodes flash at approximately 30 times per second. The diodes are switched on in sequence, with a pause with both diodes off. This allows compensation for ambient light. The microprocessor analyses the changesin light absorption during the arterial pulsatile flow and ignores the non-pulsatile component of the signal (which results from the tissues and venous blood).
Oxygen content of blood
Two forms of oxygen carriage in the blood - dissolved and Hg-O2 - make up the O2 content of (arterial) blood (CaO2). Most of the O2 content is Hg bound.
CaO2 (ml/dL) = [PaO2 x 0.003 ml/dL] + [1.34* ml O2/g Hg x Hg (g/dL) x SaO2]
CaO2 (ml/dL) = [100 x 0.003 ml/dL] + [1.34 ml/g x 15 g/dL x 1]
CaO2 (ml/dL) = 0.3 + 20 mL/dL = 23 ml/dL
CaO2 (ml/L) = 3 + 200 = 203 mL of O2 /L of blood
With average circulating blood volume of 5 L / min, the delivery of oxygen (DO2) is ~ 1000 mL/ min. This meets our metabolic needs (resting VO2 ~ 250 mL / min).
Reduced O2 delivery
Reduced content
Hypoxemia (ie reduced PaO2)
Anaemia
Interruptions to Hg binding
Insufficient cardiac output
Haemoglobin
Hg-oxygen binding demonstrates property of cooperative binding
This is due to allosteric effects (conformational change effect) of tetramer configuration
Hb-O2 binding
Hg loads and then unloads oxygen
Determinants of O2 binding:
Saturation properties: PO2 drives O2 saturation
Cooperative binding (among 4 Hg subunits)
Other factors have allosteric effects and alter the affinity for oxygen
Oxygen dissociation curve
Depicts the relationship between PaO2 and SO2
Sometimes display content of oxygen (Cao2) instead of SaO2 on the y-axis
Allosteric effectors
homo-tropic allosteric effect: the ligands are the same. The binding of O2 on one Hg subunit effects (increases) the binding of other O2 molecules to the remaining 3 subunits. This fosters the LOADING OF OXYGEN.
hetero-tropic allosteric effect: different ligands. For example the binding of CO2, H+, or 2,3 DPG to non-heme portions of the hemoglobin effects (reduces) the binding of O2 molecules to heme
H+, CO2, and 2,3 DBP stabilize the T state, fostering the RELEASE OF OXYGEN
Hb-O2 affinity altering factors
By favouring the T state, pH and 2,3 DPG alter the affinity of Hg for O2.
Temperature (non-allosteric influence on affinity) has the same effect.
These factors “shift the curve” to the right or the left.
P50 definition
The P50 (PaO2 at 50% saturation) as an index of the affinity of Hg and O2.
Foetal Hb
Foetal Hg (α2γ2) is unable to bind 2,3 DPG (which stabilizes the T state).
Thus the R state is favoured, which fosters oxygen loading.
Shift to left
Why does CO bind to Hb
CO is colourless, odourless and tasteless. Can be difficult to know when CO exposure is occurring.
Forms carboxyhaemoglobin (CO-Hb), > 200 times affinity for Hb compared to O2
Effects of CO on Hb
CO impairs both loading and unloading of O2:
O2 content is reduced due to CO outcompeting O2 for Hg binding
CO stabilizing the R state (ie left shift) for the remaining sites. This impedes release of O2.
PaO2 of blood may be normal in CO poisoning
Symptoms: headache, nausea/vomiting, dizziness/lethargy/weakness confusion coma and death (when CO-Hg > 40%)
Cyanosis
Blue-ish discoloration of skin evident in conditions of hypoxemia (low blood oxygen)
Requires a critical threshold of deoxygenated Hg
Typically correlated to a saturation < 80%
Bicarbonate
HCO3- is formed through the hydration of CO2 and subsequent dissociation of carbonic acid
CA
CO2 + H2O H2CO3 H+ + HCO3-
RBCs contain carbonic anhydrase (CA) which catalyses 1st step
2nd step happens spontaneously
HCO3- ions readily diffuse out from the RBC into the plasma
H+ ions cannot, and are buffered by Hb:
H+ + Hb.O2 H+.Hb + O2
DeoxyHb is a better proton acceptor than OxyHb (O2 unloading H+ loading)
Plasma Cl- ions diffuse into the RBC to maintain electro-neutrality (chloride shift)
Transport of CO2
Carbon dioxide transport in the blood: soluble gas (5%), carbamino compounds (5%) and bicarbonate(90%).
CO2 elimination
Easy diffusion due to high solubility constant
PvCO2 45 mmHg PACO2 40 mmHg
How can we verify CO2 elimination
If the PACO2 is 40 mmHg, what would the PaCO2 be?
The brain maintains pH and PCO2 homeostasis; when PaCO2 rises > 40 mmHg (respiratory acidosis – lecture 3 alert!) the brain triggers increased ventilation.
