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23
Gas Transport
67
Pharmacology
Undergraduate 1
12/19/2016

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Term
When PaO2 is at its normal value of 100mmHg, how much o2 is dissolved in one litre of arterial blood?
Definition
3ml
Term
Where is the remaining 197ml of o2 in that litre of arterial blood?
Definition
with haemoglobin!
Term
Describe the structure of haemolobin
Definition
consists of 4 subunits - chains of global and 4 haem groups (iron)
Term
How much o2 does one Hb molecule carry?
Definition
4
as one haem group binds one oxygen
Term
What is an o2 saturated haemoglobin called? unsaturated?
Definition
oxyhaemoglobin
deoxyhaemoglobin
Term
What does O2 binding depend on?
Definition
PO2 in surrounding fluid
high PO2 facilitates binding
low PO2 facilitates release

reversible
Term
Describe the changes when O2 binds to Fe2+
Definition
1. heme changes from dome-like to planar conformation, pulling Fe2+ downward
2. as the fe2+ moves downward, it pulls the attached histidine and F~ helix downward as well, causing Hb to switch from tensed to relaxed state
Term
Describe the changes to partial pressure caused by O2.Hb binding
Definition
when Hb binds o2, partial pressures of o2 pulmonary arteries (100mmHg) drops

more o2 can dissolve into the plasma from the alveolar air
Term
Describe transport of oxygen by haemoglobin in pulmonary capillaries
Definition
1. in the lung o2 diffuses across the respiratory membrane into the plasma, until plasma partial pressure is 100mmHg
2. it will continue to diffuse across the intracellular fluid of the RBC until partial pressure is 100mmHg
3. o2 bings to haemoglobin and partial pressure of RBC falls
4. more o2 diffuses into the ISF of RBC from the plasma
5. more o2 diffuses from alveolar air into the plasma

when blood leaves the pulmonary capillary, the PO2 is still 100mmHg
Term
Describe transport of oxygen by haemoglobin in systemic capillaries
Definition
1. po2 = 40mmHg
2. oxygen diffuses out of plasma
3. partial pressure of oxygen falls within the RBC, o2 dissociates from Hb
Term
What drives the passive diffusion of o2
Definition
the partial pressures of oxygen and the amount of oxygen bound to Hb
Term
When 100% saturated, 1g of Hb carriers ____ of o2
Definition
1.34ml
Term
What is the average Hb concentration in arterial blood?
Definition
120-170g.L-1
150 average
Term
What is the o2-carrying capacity of Hb in the blood?
Definition
average mass carried by 1g x Hb concentration in blood
1.34 x 150 = 200ml o2 per litre of blood
Term
How much O2 is delivered to tissues? per min
Definition
CO = 5L.min-1
each litre of arterial blood contains 200ml of o2
therefore 5 x200 = 100ml.min-1
Term
How much is resting o2 consumption?
Definition
250ml.min-1
Term
What happens to the rest of the 750ml.min-1 delivered?
Definition
it returns to the lungs (Hb-bound) in the venous blood and acts a large o2 'reserve', which can be released if the PO2 in the ISF and surrounding tissues falls below normal (skeletal muscle during intense exercise)
Term
How saturated is systemic artery with haemoglobin?
Definition
98%
Term
How saturated is systemic veins with haemoglobin?
Definition
75%
Term
Draw the Haemoglobin -o2 dissociation curve
Definition
sigmoidal
relationship between partial pressure of o2 and the % saturation of Hb
Term
What are points to remember on the curve?
Definition
- both start at 0 (%/mmHg)
- 40mmHg at 75%
- 98% at 100mmHg
Term
What does affinity for O2 binding depend on?
Definition
how many o2 molecules are bound
binding of one o2 molecule to one of the Hb subunits changes its conformation which increases the affinity of the other subunits for o2
Term
What causes the sigmoidal shape of the Haemoglobin-o2 dissociation curve?
Definition
positive co-operativity
one molecule binding creates a conformation change which increases binding affinity
Term
When does the Haemoglobin -o2 dissociation curve shift to the right?
Definition
decrease affinity
unloaded easier
high po2
Term
When does the Haemoglobin -o2 dissociation curve shift to the left?
Definition
increase affinity
loaded easier
low po2
Term
What are the 4 factors that affect the affinity of Hb for o2
Definition
1. temperature
2. pH
3. co2
4. 2,3-bisphosphoglycerate (2,3-DPG)
Term
How does temp affect o2 binding to Hb?
Definition
increase in temp affects the protein structure of Hb causing it to denature and thus reducing binding affinity
Term
What are the benefits of the effects of temp on o2 binding to Hb?
Definition
- increase in metabolism increases tissue temp
- this decreases the affinity of Hb for o2
- more o2 is unloaded in active tissues
- a decrease in temp as blood moves into the lungs promotes o2 loading
Term
How does pH affect o2 binding to Hb?
Definition
BOHR EFFECT
a decrease in pH decreases binding affinity
Term
What are the benefits of the effects of temp on o2 binding to Hb?
Definition
- decrease in pH in active tissues due to production of lactic acid (anaerobic) or co2 (aerobic)
- favours o2 unloading
Term
How does co2 affect o2 binding to Hb?
Definition
- carbamino effect
- co2 reacts reversibly with certain amino acids on Hb to form carbaminohaemoglobin
- HbCO2 has a lower affinity for O2 than Hb
- high PCO2 favours o2 unloading
Term
What are the benefits of the effects of temp on o2 binding to Hb?
Definition
increase in PCO2 in tissues with high metabolic rate
favours o2 unloading
Term
What is 2,3-DPG?
Definition
compound formed by an intermediate product in the glycolytic pathway in erythrocytes
Term
How does 2,3-DPG interact with O2?
Definition
o2.Hb inhibits the enzyme that produces 2,3-DPG.
so 2,3-DPG levels are low in high o2 saturation.
Term
What happens when o2 availability is reduced? e.g. high altitude
Definition
2,3-DPG levels rise
decrease Hb.O2 affinity
enhances o2 unloading in respiratory tissues (good news)
may inhibit loading of o2 in the lungs (bad news)
Term
When does 2,3-DPG effects make a difference?
Definition
once you've acclimatised to altitude
ventilation levels stabilise at higher level
beneficial effect is higher than negative
Term
What is myoglobin?
Definition
a globular protein binds o2 in muscle cells
Term
What is the use of myoglobin?
Definition
can supply o2 for a short amount of time if blood supply is cut off
only bind 1 o2 molecule
Term
Describe foetal haemoglobin
Definition
PO2 is much lower in foetuses than in adults
foetal Hb has a greater affinity for o2
this is due to structural differences in 2/4 subunits that comprise Hb molecule
Term
What shifts in Haemoglobin -o2 dissociation curve to the left?
Definition
increased affinity - o2 is loaded more easily

decreased temp
decreased [H+}
decreased presence of 2,3-DPG
Term
What shifts in Haemoglobin -o2 dissociation curve to the right?
Definition
decreased affinity - o2 is unloaded more easily

increased temp
increased [H+}
increased presence of 2,3-DPG
Term
Define hypoxic hypoxia
Definition
a low po2 in arterial blood caused by pulmonary disease
Term
Define anaemic hypoxia
Definition
reduced ability of blood to carry o2 as in anaemia
Term
Define circulatory hypoxia
Definition
a reduction in tissue blood flow by shock or local obstruction
Term
Define histotoxic hypoxia
Definition
a toxic substance interferes with the ability of the tissue to utilise available o2
Term
What is cyanosis?
Definition
a diagnostic sign of hypoxia:
- blue skin
- 5gHb/100ml arterial blood in deoxyhaemoglobin state
- occurrence in cold temp
Term
How much CO2 is bound to haemoglobin?
Definition
5% of total co2 in systemic arterial blood
7% of total co2 in mixed venous blood
Term
How much CO2 is dissolved in blood plasma?
Definition
5.5% of total co2 in systemic arterial blood
6% of total co2 in mixed venous blood
Term
How much CO2 is dissolved in form HCO3-?
Definition
89.5% of total co2 in systemic arterial blood
87% of total co2 in mixed venous blood
Term
How is the majority of co2 transported in the blood?
Definition
in the form of bicarbonate ions HCO3-
Term
How are bicarbonate ions produced?
Definition
carbonic anhydrase + CO2 + H20 = carbonic acid
carbonic acid decomposes to give bicarbonate and H+
Term
What is the effect of increased PCO2?
Definition
shifts equation to the right
increased bicarbonate ions
increased H+ in the blood
Term
What is the effect of decreased PCO2?
Definition
shifts equation to the left
decreased bicarbonate ions
decreased H+ in the blood
Term
What is the role of carbonic anhydrase?
Definition
drives the equation to equilibrium within the red blood cell
acid-base balance
Term
Describe co2 transport in the systemic capillaries
Definition
PCO2 = 46mmHg

1. co2 is produced and diffuses via the ISF, into the plasma in systemic capillaries, increase PCO2
2. co2 diffuses into RBC where it is converted into HCO3- and H+ (catalysed by carbonic anhydrase)
3. H+ are buffered by Hb (promotes unloading of O2)
4. HCO3- is swapped for a Cl- (chloride shift) to avoid inhibition of the reaction (equilibrium)
Term
Describe co2 transport in the pulmonary capillaries
Definition
PCO2 = 40mmHg

1. co2 diffuses into alveolar air and therefore co2 levels fall
2. loss of co2 causes bicarbonate ions and H+ in RBC to reform to co2 and h2o
3. co2 diffuses out to alveoli
4. hco3- in roc decreases causing hco3- to be exhcanged for cl- in roc and more co2 can be exhaled
Term
How much co2 is produced every min?
Definition
cellular respiration produces 200ml of co2 per min
Term
Describe the Haldane effect
Definition
binding of o2 to Hb reduces the ability of Hb for co2
when PO2 rises, more co2 is unloaded from Hb where it can diffuse into the alveolar air
Haldane effect increases the rate of co2 elimination in the lungs
Term
Describe respiratory acidosis
Definition
blood pH below 7.35
hypoventilation
high PCO2
Term
Describe respiratory alkalosis
Definition
blood pH above 7.45
hyperventilation
low PCO2
Term
Define aneamia
Definition
a decrease in the o2-carrying capacity of the blood
gerenally associated with a low haematocrit
Term
What is nutritional anaemia?
Definition
caused by dietary deficiency - most commonly iron (which decreases Hb synthesis) or folic acid (which inhibits DNA synthesis and cell division)
Term
What is pernicious anaemia?
Definition
caused by deficiency of intrinsic factor (required for the absorption of vitae's B12), lack of which inhibits DNA synthesis and cell division
Term
What is aplastic anaemia?
Definition
caused by defect in the bone marrow, the primary site of RBC production
Term
What is renal anaemia?
Definition
caused by decreased EPO production in kidneys (renal disease) resulting in decreased RBC synthesis
Term
What is haemorrhagic anaemia?
Definition
followed by rapid blood loss, fluid shifts into the vascular compartment restores blood volume within a few days, but abc levels take weeks to return to normal
Term
What is haemolytic anaemia?
Definition
caused by the rupture (haemolysis) of RBC caused by malaria or sickle cell
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