General Gas Transport by the blood I Questions Flashcards
How is O2 carried in the blood?
Dissolved in plasma - 3%
In chemical combination with Hb (HbO2) - 97%
How much Hb does normal blood contain?
In anaemia?
In polycythemia?
Normal blood has 150gHb/L blood
Example values:
Anaemia = 100gHb/L (or less)
Polycythaemia = 200gHb/L
Hb: How many per RBC? What is Hb structure?
~280 million Hb molecules per RBC
Hb structure:
Two alpha chains
(important in alpha thalassemia)
Two beta chains
(important in beta thalassaemia. B chains also bind BPG)
Four Heme groups containing Fe-
What is co-operative binding of HbO2
First O2 molecule is difficult
But the binding of 1st creates a conformational change which facilitates the binding of the 2nd and 3rd molecules
4th is again harder, partly due to crowding of the Hb molecule, and partly due to O2’s natural tendency to dissociate
What is HbO2 saturation at a PO2 of…
100mmHg
60mmHg
40mmHg
27mmHg
100mmHg - 97-98% saturation
60mmHg = 88%
40mmHg - 75% saturation
27mmHg - 50%saturation (this is the P50 for Hb - during left shift)
*Note P50 under Right shift conditions is higher: 35mmHg
Calculate the delivery of O2 to the tissues for…
Normal blood at 75% HbO2 saturation
Anaemic blood at 75% HbO2 saturation
Polycythemic blood at 75%O2 saturation
…
@75% = ~150mls O2 per L blood
What is the resting O2 requirement for the tissues?
What is resting cardiac output?
At rest = ~250ml/min
CO at rest = ~5L/min
Describe short term compensation for high altitude
Occurs in response to the low PO2 at altitude
Low PO2 sensed by peripheral chemoreceptors
Feedback to Respiratory centre in medulla oblongata leads to an increase in ventilation
However, the increase in ventilation also decreases PCO2 (respiratory alkylosis).
Central chemoreceptors respond to the decrease in PCO2. Regulation takes priority over PO2 in this scenario.
Feedbacks from CCs to the Respiratory centre cause decreased ventilation.
Describe Acclimatisation to Altitude
What are some of the eventual physiological changes that occur in response to altitude
Respiratory Alkylosis compensation takes 12-36 hours:
Body compensates for respiratory alkylosis via renal excretion of HCO3-
Eventual physiological changes:
Decreased lactate production
Polycythemia (haematocrit)
Increased RBC mass
Increased concentration of capillaries in skeletal muscle
Increased myoglobin stores
Hypoxic vasoconstriction (e.g. only perfusing bases of lung)
Increased pulmonary artery pressure to increase oxygenation of more blood
What is the drop in venous PO2…
At altitude with a starting alveolar PO2 of 60mmHg
During deep sea diving with an alveolar PO2 of 500mmHg
At 60mmHg, Hb is still 88% saturated.
Given that, at rest, the body requires ~50ml)2/L, the venous return will still have a PO2 of ~35mmHg. Only a 5mmHg drop.
At alveolar PO2 of 500, the Hb can only get to 100% saturation.
At rest, with 50ml/L blood O2 consumption….this leaves us with a venous return PO2 of 45mmHg. Only a 5mmHg rise.
Define HbO2, PO2, and O2 content.
What are each affected by?
HbO2 = O2 bound to Hb. 97% of O2. Associated/things that need to be taken into account: Left and Right shift events. Hb concentration in blood. PO2.
PO2 = O2 dissolved in plasma. 3% of O2.
Things to be taken into account:
The partial pressure and solubility of O2 (henry’s law)
O2 content = HbO2 + PO2
CO and Hb…
Lethal dose?
CO binds to Hb at the same place as O2 (heme group, Fe-) but with much more affinity - 200x that of O2.
As little as 0.6mmHg of CO can be lethal
CO + Hb = carboxyhaemoglobin
Blood still red
Thus, severe hypoxia occurs without cyanosis
Does not affect PO2
How can you tell if someone has CO poisoning?
What other use does CO have?
CC-oximeter - detects presence of CO bound to Hb
Administering small amounts of CO can help to determine diffusion capacity. A certain small amount is administered. Knowing that it has a higher affinity for Hb than O2 thus will be taken up preferentially, thus reflecting diffusion capacity.
Amount of CO exhaled is then measured.
Treatment of CO poisoning
Administer 100% O2
High doses of O2 help to displace CO, and shorten CO’s half-life
Factors that cause Left Shift. When does this occur (normally)?
What is the P50 during left shift? Why?
‘Left shift’ typically occurs in the lungs in response to…
Decreased H+ Decreased CO2 Thus Increased pH (alkylosis) Decreased Temperature Decreased BPG
P50 during left shift = 27mmHg
Because left shift causes increased O2Hb binding capacity. Thus, lower PO2 can maintain 50% HbO2 saturation
Factors that cause Right Shift. When does this occur (normally)?
What is P50 during Right shift? Why?
‘Right Shift’ typically occurs at the tissues in response to…
Increased H+ Increased CO2 Thus Decreased pH (Acidosis) Increased Temperature Increased BPG P50 during right shift = 35mmHg
Because right shift causes decreased HbO2 affinity, a higher PO2 is required to maintain 50% HbO2 saturation
What is the Bohr effect?
The Bohr effect explains the relationship between pH (CO2/H+) and Hb-O2 affinity.
Acidosis (decreased pH) results in decreased binding affinity between Hb and O2 (Right Shift)
Alkalosis (increased pH) results in increased binding affinity between Hb and O2 (Left Shift)
What is the significance of increased temperature causing a right shift?
Useful in certain states such as exercise, where you need increased O2 offloading at the tissues.
Most of the effects of exercise promote a right shift:
Increased temperature
Increased metabolism (increases CO2 and thus also decreases pH)
Release of metabolic acids (decreases pH)
What is BPG? How does it affect curve shifts?
What is the normal concentration of BPG in RBCs?
BPG is an end-product of RBC metabolism (glycosis)
BPG interacts with B chain of Hb, causes a right shift, decreased HbO2 affinity
Normal BPG is normally present at a concentration of ~15mmol/gHb
Without this concentration, offloading of O2 at the tissues would be impaired
What causes an increase or a decrease in BPG?
BPG in increased by Hypoxia: e.g. COPD, High altitude. This aids O2 offloading at tissues
BPG binds to B chains of Hb
BPG is decreased in stored bloods such as transfusion bloods
What is HbF?
What is P50 for HbF?
HbF = foetal Hb
Has an increased binding capacity for O2
Is in a kind of constant left shift
HbF does not have B chains - Has gamma chains instead. Thus, BPG does not bind as readily - cannot cause its’ right shift.
HbF P50 = 19mmHg
Even LOWER PO2 is requires for 50% Hb saturation
Newborns have both HbF and HbA
HbF decreased by ~ 6 months
When does L or R shift have most effect?
L and R shifts have little effect along the upper, flatter portion of the Hb dissociation curve.
Have more effect on the steeper portion of the curve.
Significance of curve shifts against a backdrop of lung disease?
What kinds of events might cause Right shift and thus hypoxia in a lung disease state?
Lung disease states are often characterised by low PO2
E.g. arterial PO2 might be 60mmHg.
This is ok under normal conditions, at rest, because Hb saturation is still ~88% (which is adequate to deliver O2 to tissues). This is due to the flat portion of the curve.
However, any Right Shift that occurs in addition to the already low (hypoxic) PO2 will push the Hb saturation / PO2 into the steep portion of the curve, and result in impaired O2 delivery to the tissues.
Right shift state might be caused by
Exercise
Any condition resulting in CO2 retention (decreasing pH - acidosis)
Definition of Hypoxia?
Occurs when there is insufficient O2 for tissues to maintain adequate aerobic metabolism.
This results in increased anaerobic metabolism, which decreases pH further, resulting in acidosis, and further Right Shift.
What types of Hypoxia Classifications are there? What causes them?
Hypoxic Hypoxia:
Due to low arterial PO2: high altitude, alveolar hypotension, decreased lung diffusion capacity, abnormal V/Q ratio
Anaemic Hypoxia:
Due to decreased total O2 bound to Hb: blood loss, anaemia, altered Hb-O2 binding - e.g. CO poisoning
Ischaemic Hypoxia:
Due to reduced blood flow: HF, Shock, Thrombosis/Embolism, Atherosclerosis
Histotoxic Hypoxia:
Failure of O2 to be used by cells. E.g. cyanide poisoning, or other metabolic poisons
What are the O2 Transport Reserve Mechanisms in response to Hypoxia?
Pulmonary reserve - Increase Ventilation
Circulatory Reserve - Increase CO2 to increase O2 offloading at tissues
Erythropoietic reserve - Increase in RBC production (polycythemia) to increase Hb and thus O2 carrying capacity
Chemical Reserve - Left/Right shift factors
