Lecture 2 - Role Of Heamoglobin In O2 Delivery To Tissues

Question 1

Transport of oxygen from pulmonary capillaries to tissues

Answer 1

• usual arterial PO2 is 100mmHg
• PO2 of interstitial fluid is variable in different tissues but averages about 40mmHg
• since O2 is always being used by the cells, the intracellular PO2 remains lower than interstitial fluid
• partial pressure gradient from interstitial fluid to tissues drives diffusion of O2 into the cell

Question 2

Most oxygen is transported in blood bound to hemoglobin

Answer 2

• O2 is either physically dissolved or bound to hemoglobbin molecules within erythrocytes
• at a PO2 of 100 mmHg only 3 ml O2 can dissolve in 1L of blood
• at a normal cardiac output of 5L/min, only 15 ml O2 can be delivered to the tissues in this form
• normal O2 consumption at rest is 250 ml/Min
• 98.5% of O2 is bound to hemoglobbin
• normal blood can carry > 204 ml O2/litre via Hb
• 5L/min blood can carry 1020ml/min O2, which is 60-70x greater than that of plasma alone

Question 3

Erythrocytes carry hemoglobin

Answer 3

• erythrocytes make up 45% of blood volume
• there are 5 billion RBC per ml blood
• a RBC is 8 um in diameter
• no nucleus, no DNA -> survive over 4 months
• each RBC contains more than 250 million hemoglobin molecules

Question 4

Hemoglobin molecule

Answer 4

• globin portion: protein made up of 4 highly folded polypeptide chains
• four non-protein heme groups, each bound to one polypeptide
• each heme consists od an iron molecule in a porphyrin
• each of the four iron molecules can bind reversibly with one molecule O2
• each Hb molecule can bind to four O2 molecules
• colour change from to dark red to bright red

Question 5

Cooperative binding of oxygen to hemoglobbin

Answer 5

• when oxygen binds to the iron, it causes the iron to move in the porphyrin ring, changing the conformation of the Hb molecule
• Hb has 2 states: the T state (tense) and the R state (relaxed)
• Hb has a lower affinity for O2 in the T state
• once a molecule of O2 binds to Hb, the conformation changes to the R state and Hb’s affinity increases for binding more oxygen

Question 6

Anemia effect on O2 concentration and saturation

Answer 6

• doesnt change saturation

- but decreases maximal O2 concentration

Question 7

Features of the Oxygen-Hb dissociation curve

Answer 7

• flat between Po2 of 70-100mmHg: an increase in PO2 to above 100mmHg has little effect on O2 content, and small decrease in PO2 have little effect on arterial blood O2 content
• steep in tange 10-50 mmHgL blood in capillaries of metabolically active tissue has a PO2 in that range: small changes in PO2 produce large changes in O2 binding to Hb

Question 8

Utilization coefficient

Answer 8

• the PO2 of mixed venous vlood in a resting man is about 40mmHg which is about 75% saturated
• at rest, only about 5ml O2 (out of 20) is extracted per 100 ml blood
• utilization coefficient is about 25%: this can increase greatly during exercise

Question 9

O2-Hb dissociation curve is altered by metabolites and temperature

Answer 9

• increase in PCo2 or a decrease in pH shifts O2-Hb curve to the right: unloading more O2 at same PO2: this occurs when metabolic activity increases
• increase in temp has the same effect, as when metabolic activity increases
• BPG is a constituant of RBC which also shifts the curve to the right. Levels of BPG increases in chronic hypoxia and thus also favours increased oxygen unloading, ass when metabolic activity icnreases

Question 10

Symptoms of CO poisoning

Answer 10

• hallucinations
• listlessness
• delirium and emotional disturbances
• depression
• sudden death with no apparent cause

Question 11

Oxygen binding sites on hemoglobn have a much higher affinity for CO than for oxygen

Answer 11

• binds to Hb at O2 binding site to form carboxyhaemoglobin
• affinity for Hb for Co is 200 times that for O2
• a small amount of CO can make Hb unavailable for binding with O2 - causes tissue Hypoxia
• but doesnt cause the sensation of breathlessness? Why not

Question 12

Hypoxic hypoxia

Answer 12

• failure of adequate O2 to reach the blood in the lungs

- inadequate O2 in the atmosphere, obstruction of airways, thickening of alveolar-capillary membrane (pulmonary oedema)

Question 13

Stagnant hypoxia

Answer 13

• failure to transport sufficient O2 to tissues because of an inadequate blood flow
• low cardiac output following heart failrue or circulatory shock, tourniquet, peripheral oedema

Question 14

Anaemic hypoxia

Answer 14

• O2 carrying capacity inadequate for O2 demand of body

- anaemia, CO poisoning

Question 15

Histotic Hypocia

Answer 15

• failure of tissues to utilize O2 even though adequate quantities are delivered
• causes: cyanide poisoning. Enzymes responsible for O2 utilization are blocked

Question 16

Most CO2 is transported in the blood as bicarbonte ions

Answer 16

• 3 forms of CO2 transport: physically dissolved, bound to Hb, bicarbonate ions
• amount of CO2 physically dissolved is directly proportional to the PCO2. CO2 is more soluble than O2 but only 10% is in physical solution
• about 20% combines with Hb to form carbamino heamoglobbin: different binding to O2. Reduced Hb has a greater affinity for CO2 than HbO2, therefore unloading of O2 in tissues facilitated uptake of Co2 by Hb
• most CO2 is carried in form of bicarbonate ions, and this reaction is greatly accelerated by presence of carbonic anhydrase in RBC

Question 17

Suite

Answer 17

• as this reaction proceeds, HCO3-1 and H+ accumulate inside the RBC
• membrane of a cell is highly permeable to HCO3-, bit not H+
• most of the accumulated H+ in the cell becomes bound to Hb
• reduced Hb has a greater affinity for H+ than HbO2 - therefore unloading of O2 facilitated the uptake of H+ ions by Hb
• because only free dissolved H+ ions contribite to pH, this means that the venous vlood is considerably less acid than it otherwise would be
• removal of O2 from Hb incfreases the ability of Hb to puck up CO2 and H+ generated by the reaction of CO2 with H2O: Haldane effect
• Bohr and haldane effect work together to facilitate O2 reelase and Co2 and H+ uptake in tissues

Question 18

VQ mismatch are likely to have a more detrimental effect on PaO2 than on PaCO2

Answer 18

• CO2 carrying capacity&raquo_space; O2 carrying capacity
• CO2 carrying capacity increases almost linearly with increase PCO2 in physiological range
• blood leaving under-ventilated areas of lung will have a CO2 content that is high and blood leaving overventilated areas of lung will have a CO2 content that is low: overall this may balance out and CO2 content is likely to be normal
• blood leaving underventilated areas of lung will have an O2 content that is low and blood leaving overventilated areas of lung will have an O2 content that is normal. Overall after mixing, O2 content of blood is likely to be low