Oxygen transport Flashcards
oxygen systemic arterial partial pressure
between 75mmHg- 100mmHg, 14kPa
how is oxygen carried in the blood?
small volume dissolves in blood, other becomes bound to haemoglobin
what is haemoglobin?
protein of a molecular weight of 64,500
4 globin subunits, 2 alpha and 2 beta chains, each 16KDa
one haem structure in each chain that binds to oxygen
explain haem structure
four pyrrole rings held together by methane bridges
centre of the pyrrole rings is a bivalent iron ion, held together by two ionic and two covalent bonds
oxygen binds reversibly to the iron ion with no change in valency, so the reaction is called oxygenation and not oxidation
haemoglobin function
carries 4 oxygen molecules to form oxyhemoglobin
O2 carrying capacity definition
the maximum amount of oxygen that can be combined with Hb which is limited by the number of binding sites and whether they are available
2 measurements of bound oxygen
oxygen concentration as ml O2/100ml of blood
percentage saturation of maximal oxygen capacity
what process occurs during the binding of oxygen atoms
positive cooperativity
explain positive cooperativity
binding of each oxygen molecule to the tetramer facilitates the binding of the next molecule which results in a sigmoidal dissociation curve
- first oxygen difficult to bind
- once first binds, conformation change occurs bringing forward the pyrrole groups, makes it easier for the next 2 to bind
- last one more difficult, as smaller chance that it binds to an unoccupied binding site
what does the curve facilitate?
unloading of oxygen at tissues where partial pressure is low
loading at the lungs where partial pressure is high
curved S shape advantages
flat upper portion means that if PO2 falls slightly that loading is hardly affected
central steep part of the curve means that peripheral tissues can withdraw large amounts of oxygen for only a small drop in capillary partial pressure
oxhaemoglobin saturation definition
haemoglobin is said to be saturated with oxygen when all four binding sites are occupied
factors affecting oxygen binding to haemoglobin
- increase in H+
- increase in PCO2
- temperature
- increase in 2,3 diphosphoglycerate
explain the resulting shift of the curve
rightward shift
favour unloading the oxygen, with more oxygen unloaded at a given partial pressure of oxygen within the tissue capillary
what is a name for this + definition?
Bohr Effect
shifting to the right due to the collective effect of partial carbon dioxide pressure and decrease in pH
allosteric binding of carbon dioxide
increase in H+ ions, protonate various amino acid residues, such as histidine allowing them to form ion pairs that stabilise the deoxyhaemoglobin in the T state
bohR Right
explain 2,3-diphosphoglycerate effect
2,3-DPG is produced by red blood cells during glycolysis and binds to Hb
this reduces the affinity for oxygen and favours unloading
2,3-DPG concentrations increase during hypoxic conditions, favouring the delivery of oxygen to tissues
heteroallosteric effector of haemoglobin that lowers its affinity for oxygen by binding preferentially to deoxyhaemoglobin, thus favouring the formation of T haemoglobin
explain the temperature effect
increases in temperature begin to denature the haemoglobin, weakening the bonds between iron and oxygen
with an increase in temperature there is also an increase in partial oxygen pressure, so for a lessen haemoglobin saturation there is a higher partial pressure of oxygen
what is methemogloinaemia ?
a form of abnormal haemoglobin where the iron centre has been oxidised from +2 to +3, causing a leftward shift of the curve as the ions are unable to unload the bound oxygen into the tissues, as +3 impairs cooperativity
thereby increasing its affinity for oxygen
what can methemoglobin be used for?
has an increased affinity for cyanide
administration of a nitrite will oxidise the haemoglobin to raise methemoglobin levels so that they can bind to cyanide and remove it
inadequate oxygen uptake of tissues causes
- hypoxaemia- low arterial partial pressure and percentage arterial saturation due to low inspired oxygen, diffusing capacity of V/Q mismatch, Not enough oxygen
- stagnant hypoxia- low perfusion, cardiac failure. blood oxygenated, but not enough of it.
- anaemic hypoxia, low Hb, carbon monoxide poisoning. There is enough oxygen but the body cannot carry it
- histotoxic hypoxia, high venous pressure and saturation due to inability of tissues to use oxygen, cyanide poisoning . There is enough oxygen but the body cannot use it
how does cyanide poison?
acts as an inhibitor of enzyme cytochrome C oxidase in the electron transport chain by attaching to the iron
prevents the transport of electrons from cytochrome C to oxygen and thus causes histotoxic hypoxia
hypoxia definition
a condition in which the body or region of the body is deprived of adequate oxygen supply at the tissue level
hypoxemia definition
an abnormally low level of oxygen in the blood
body’s oxygen stores
lungs, blood, tissue fluid, muscle myoglobin
what affinity does carbon monoxide have for Hb?
240x that of oxygen
What does the saturation curve look like for carbon monoxide?
identical in shape but the PCO acts is greatly compressed due to better binding at lower partial pressures
Why is CO bad?
binds irreversible to form carboxyhaemoglobin which shifts the oxygen curve to the left and interferes with the unloading of oxygen
