4.1 slide 19 onwards INCOMP Carriage of oxygen in the blood Flashcards
At PO2 of 100mmHg (13.3 KPa) how much only dissolves in plasma ?
0.13mmol/l
Because oxygen is poorly soluble in plasma the amount of dissolved oxygen is insufficient to meet the demands of the body therefore what do we require ?
a chemical reaction to transport more oxygen per litre of blood
Why is there more CO2 in plasma than oxygen ?
solubility of CO2 in blood is about 20x that of O2 therefore more CO2 than O2 is present in plasma at equal partial pressures
CO2 reacts chemically with water
What are the 2 jobs of the cardiovascular system ?
- supply oxygen and metabolic fuel (e.g. glucose) to tissues and to take away the waste products of metabolism (e.g. CO2)
- maintain defenses against invading micro-organisms
What’s the equation that partial pressures of resp gases can be expressed by ?
Partial pressure of gas (A) = total pressure in gas mixture x fractional concentration of (A)
Why is carriage of oxygen a problem ?
oxygen is a powerful oxidising agent
most organic molecules are damaged by too high a concentration of O2
erythrocytes are specially designed to carry O2
Ability to transport oxygen without being oxidised depends on what ?
ability of the iron atom to be hexavalent (form 6 bonds with surrounding atoms)
In ferrous iron (Fe++) what does the atom have ?
6 unpaired ‘d’ orbital electrons which can therfore form bonds with 6 electrons from other atoms
where 4 of the orbital electrons are in a plane and 2 protrude above and below the plane (think Alvl chem!)
The four iron electrons in the plane are held by four covalent bonds to nitrogen atoms in a molecule is called =
a porphyrin ring
What is the porphyrin ring together with its ferrous iron centre called ?
haem group
Where in haemoglobin does the weak reversible bond form ?
between oxygen and the 6th ferrous electron
Why is the bond between oxygen and the sixth ferrous electron in hemoglobin considered weak?
The oxygen molecule can’t get close enough to the iron atom to fully remove the electron due to steric hindrance from other parts of the haemoglobin molecule
How does steric hindrance affect the oxygen-iron bond in hemoglobin?
It weakens the oxygen-iron bond in hemoglobin
by preventing the oxygen molecule from getting close enough to the iron atom to strongly bind and fully remove the sixth ferrous electron
What is the significance of the reversible bond formed between oxygen and hemoglobin’s iron atom?
reversibility of the bond is crucial for oxygen transport, allowing hemoglobin to pick up oxygen in the lungs and release it in tissues where it is needed
What is human haemoglobin made up of ?
4 subunits , each with haem prosthetic group attached
4 polypeptide chains bound to each other by salt bridges, hydrogen bonds, hydrophobic interactions.
Regarding proper oxygen transport what of the haemoglobin structure is vital ?
the exact way that the 4 subunits with a haem prosthetic group fit together
What creates the ‘steric hindrance’ which ensures that the oxygen molecule cannot get physically close enough to the iron to remove the electron ?
3 dimensional folding of the subunits
What is oxygen bonding critically dependent on ?
- interlocking of haem subunits
- partial pressure of oxygen in solution
When the partial pressure is high (lungs) , the oxygen binds and we have …1….
In the tissues the oxygen dissociates to form …2… which is transported back to the lungs for ..3..
- oxyhaemoglobin
- deoxyhaemoglobin
- reoxygenation
What happens if the steric hindrance is not quite right ?
oxygen does oxidise the iron in the haemoglobin to its ferric state
resulting in formation of methaemoglobin which can’t carry oxygen
What does the ferric iron in methaemoglobin no longer have ?
the 6th electron to attract the oxygen molecule
why is the gradual formation of methaemoglobin unavoidable ?
steric hindrance that allows reversible bonding of oxygen to haeme iron but not actual oxidation of the iron is so finely balanced
In newly formed red blood cells what happens to most of the methaemoglobin formed ?
it’s converted back to haemoglobin by the NADH-dependent enzyme found inside the cell
= methaemoglobin reductase =
When do the amount of methaemoglobin increase ?
as cells age
Apart from cells aging, what else reduces steric hindrance and causes iron oxidation ?
- structural impairment of haemoglobin
- deficiency of methaemoglobin reductase
What is one of the signals that result in the removal of exhausted red cells and why ?
They are thought to be removed from circulation due to a rise in the level of methamoglobin in the cell
causing markers on the surface of the red cell to change
this change is detected by cells in the liver and spleen which remove these exhausted red cells
What is 2,3 DPG ?
2-3 diphosphoglycerate = a small separate molecule bound loosely to the haemoglobin molecule
How does 2,3 DPG interact with the hemoglobin molecule when the beta subunits begin to deoxygenate?
2,3 DPG binds more tightly to them and moves into the center of the hemoglobin molecule
What effect does 2,3 DPG have on oxygen release from hemoglobin?
2,3 DPG increases the rate of oxygen release from hemoglobin, enhancing the ability of red blood cells (RBCs) to release oxygen in hypoxic tissues
ensuring that tissues with low oxygen levels receive more oxygen
How does the binding of 2,3 DPG to hemoglobin affect its structure?
auses it to move into the center of the hemoglobin molecule, which helps to increase the rate of oxygen release
What is the significance of 2,3 DPG in red blood cells under hypoxic conditions? [change / remove Q ? ]
2,3 DPG plays a critical role in red blood cells under hypoxic conditions by enhancing oxygen release from hemoglobin, allowing tissues with low oxygen levels to receive more oxygen
What does acidosis inhibit in the red cell?
glycolysis
- What happens to 2,3-DPG concentration when pH is low ?
- happens because of what ?
- conc falls
- acidosis inhibits red cell glycolysis
List 3 factors that can increase the concentration of 2,3-DPG :…
- thyroid hormones
- growth hormones
- androgens
proportion of haemoglobin that is bound to oxygen is called what ?
percent saturation
How is percent saturation written as ?
% Hb saturation or often for arterial blood as SaO2
what is percent saturation easily measured with ?
a pulse oximeter
(1) What range of values of oxygen saturation should healthy individuals at sea level be ? (2) and what should it be above ?
- 96% and 99%
- 94%
An arterial oxygen saturation value below 90% is known as ?
hypoxaemia
WHy does the oxygen saturation not directly reflect tissue oxygenation ?
the ability to unload the oxygen in the respiring tissues determines the oxygen delivery
What is the oxygen unloading described by ?
oxygen-haemoglobin dissociation curve
What is shape of oxygen/haemoglobin dissociation curve ?
’s’ shaped
flat at high pO2 and steep at medium and low pO2
what does the flat upper part of a oxygen/ haemoglobin dissociation curve mean ? & give a range (mmHg values)
Hb is more than 90% saturated by oxygen over a wide range of pO2 in the lungs from 70 mmHg to > 100mmHg
what does the steep middle part of a oxygen/ haemoglobin dissociation curve mean ? & give a range (mmHg values)
Hb releases large amounts of oxygen for a small decrease in pO2 over the range 20-40 mmHg
slide 19 onwards..
