General Gas Transport by the blood I Questions

Question 1

How is O2 carried in the blood?

Answer 1

Dissolved in plasma - 3%

In chemical combination with Hb (HbO2) - 97%

Question 2

How much Hb does normal blood contain?

In anaemia?

In polycythemia?

Answer 2

Normal blood has 150gHb/L blood

Example values:

Anaemia = 100gHb/L (or less)

Polycythaemia = 200gHb/L

Question 3

Hb: How many per RBC? What is Hb structure?

Answer 3

~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-

Question 4

What is co-operative binding of HbO2

Answer 4

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

Question 5

What is HbO2 saturation at a PO2 of…

100mmHg

60mmHg

40mmHg

27mmHg

Answer 5

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

Question 6

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

Answer 6

…

@75% = ~150mls O2 per L blood

Question 7

What is the resting O2 requirement for the tissues?

What is resting cardiac output?

Answer 7

At rest = ~250ml/min

CO at rest = ~5L/min

Question 8

Describe short term compensation for high altitude

Answer 8

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.

Question 9

Describe Acclimatisation to Altitude

What are some of the eventual physiological changes that occur in response to altitude

Answer 9

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

Question 10

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

Answer 10

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.

Question 11

Define HbO2, PO2, and O2 content.

What are each affected by?

Answer 11

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

Question 12

CO and Hb…

Lethal dose?

Answer 12

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

Question 13

How can you tell if someone has CO poisoning?

What other use does CO have?

Answer 13

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.

Question 14

Treatment of CO poisoning

Answer 14

Administer 100% O2

High doses of O2 help to displace CO, and shorten CO’s half-life

Question 15

Factors that cause Left Shift. When does this occur (normally)?

What is the P50 during left shift? Why?

Answer 15

‘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

Question 16

Factors that cause Right Shift. When does this occur (normally)?

What is P50 during Right shift? Why?

Answer 16

‘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

Question 17

What is the Bohr effect?

Answer 17

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)

Question 18

What is the significance of increased temperature causing a right shift?

Answer 18

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)

Question 19

What is BPG? How does it affect curve shifts?

What is the normal concentration of BPG in RBCs?

Answer 19

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

Question 20

What causes an increase or a decrease in BPG?

Answer 20

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

Question 21

What is HbF?

What is P50 for HbF?

Answer 21

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

Question 22

When does L or R shift have most effect?

Answer 22

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.

Question 23

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?

Answer 23

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)

Question 24

Definition of Hypoxia?

Answer 24

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.

Question 25

What types of Hypoxia Classifications are there? What causes them?

Answer 25

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

Question 26

What are the O2 Transport Reserve Mechanisms in response to Hypoxia?

Answer 26

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