Carriage of Oxygen in the Blood Flashcards
why is carrying oxyen around in the blood a potential problem?
what is oxidation and reduction?
which reaction in body is key ox / reduction reaction?
- oxygen is a very powerful oxidising agent: most organic molecules are damaged by too high a concentration of O2
- oxidation: is a loss of electrons. oxidising agent: combine with other atoms & remove electrons from the oxidised molecule. releases energy
- reduction: process of adding electrons. reducing agent: combine with other atoms and add electrons (often requires energy)
- The NAD/NADH system can be thought of like a bank with electrons as money. The bank can give you money (NAD can give you an electron), or you can save money by storing an electron (by giving up an electron or two to NAD+. NAD+ + H+ + 2e- NADH
for reactions needing energy / elecrons: NADH -> NAD+ + H+ + 2e-
when plenty of energy: NAD+ + H+ + 2e- -> NADH
how does Hb bind to o2?
erythrocyte shape? and size? characterisitics?
Haemoglobin can reversibly bind to O2, without becoming pernanently damaged
- *erythrocytes**:
- no nuclei
- no mt
- biconcave discs,
- about 7 micrometres in diameter
- 2 micrometres thick.
- volume of about 90 cu mm (1 cu mm = 1 femtolitre)
what is microcytic anaemia?
what is macrocytic anaemia?
- *microcytic anaemia:** red cell is smaller than usual
- *macrocytic anaemia:** red cell is larger than usual
what are immature rbc known as? after how long do they turn into mature rbc?
where found?
what % of circulating blood are they?
why called their name? how do u spot?
what dye?
reticulocytes
- 1-2% of circulating rbcs
- change into rbc after a day of circulating
- found just before and after leaving bone marrow
- called reticulocytes because of a reticular (mesh-like) network of ribosomal RNA (to make the Hb) that becomes visible under a microscope with certain stains such as new methylene blue
how do RBC produce ATP?
what does this mean regarding RBC pH?
- RBC dont have mitochondria
- RBC produce ATP by glycolysis (glucose -> pyruvate -> lactic acid)
- due to lactic acid = low pH
what glucose uptake system do RBC use?
why do RBC need glucose?
what do RBC use to protect agaisnt oxidative damage?
what is Hb gradually converted to in the rbc?
typical life span of rbc? what changes throughout lifespan?
RBC use Glut1: faciliated diffussion. not regulated by insulin
RBC need glucose to maintain sodium pumps in cell membrane
Red cells contain antioxidants/reducing agents, like Vitamin C, to protect them against oxidative damage BUT: This is also taken up from the blood by Glut1. However, they are progressively damaged by the oxygen they carry. The haemoglobin is gradually converted to methaemoglobin (oxidised haemoglobin)
lifespan:
The lack of repair ability means that the red cells have a limited lifetime, typically about 120 days. The ageing erythrocyte undergoes changes in its plasma membrane, making it susceptible to recognition by phagocytes and subsequent phagocytosis is the spleen, liver and bone marrow
explain the bonding that occurs in Fe 2+ in RBC
what is a haem group?
- The ability to transport oxygen without being oxidised depends on the ability of the iron atom to be hexavalent, which means form 6 bonds with surrounding atoms
- In ferrous iron, Fe2+, the atom has 6 unpaired d orbital electrons and can therefore form bonds with 6 electrons from other atoms
- four iron electrons in the plane are held by 4 covalent bonds to nitrogen atoms in a molecule called the porphyrin ring
- The porphyrin ring, together with its ferrous iron centre, is called a haem group
- A histidine group underneath the porphyrin ring binds a fifth electron. This leaves one electron that can react with other molecules
- In haemoglobin, oxygen forms a weak irreversible bond with the 6th electron. The bond is weak, (as the oxygen molecule cannot get close enough to the iron to fully remove the electron due to steric hindrance from other parts of the haemoglobin molecule)
explain structure of human haemoglobin?
what is steric hindrance? what does this mean?
- made up of **4 subunits, each with a haem prosthetic group attached
- Adult Hb is normally made up oftwo a subunits and two b subunits =** This is haemoglobin A.
- Other subunits can exist, for example the g (gamma) subunit.
- The three dimensional folding of the subunits creates ‘steric hindrance’ so the oxygen molecule cannot physically get close enough to the iron to remove the electron, thus making the bond oxygen has with this haem group reversible
THEREFORE:
oxygen is attracted to the iron, but does not get close enough to oxidise it.
what is strucutre of fetal Hb ? why important?
Foetal haemoglobin: two g subunits and two a subunits.
Foetal haemoglobin has a higher affinity for oxygen than the adult haemoglobin, and thus can remove it from the placental blood at the lower partial pressure.
what happens to Hb when partial pressure of O2 is high (e.g. in lungs) and low (in tissues)
- when partial pressure of oxygen is high (i.e. the lungs), the oxygen binds and we have oxyhaemoglobin
- In the tissue (as the partial pressure of oxygen is lower), the oxygen dissociates to form deoxyhaemoglobin which is transported back to the lungs for reoxygenation.
what happens if steric hindrance is not correct? what are the consequences of this?
- If the steric hindrance is not quite right, oxygen DOES oxidise the iron to its ferric state
- Haemoglobin with ferric iron is called methaemoglobin and cannot carry oxygen. The ferric ion is methaemoglobin no longer has the 6th electron to attract the oxygen molecule
why do RBC have a limited lifespan?
what repair can be done to RBC - by what?
what is methaemoglobinemia? caused by (2)
- RBC gradually accumulate methaemoglobin and then cannot carry oxygen = limited lifespan
- initially, only 1 of the subunits haem groups is ferric ion & so only 3 02 is carried instead of 4.
- methaemoglobin reductase can do some repair: methaemoglobin -> haemoglobin. occurs in early life of RBC, but gradually the methaemoglobin builds up too much. NEEDS NADH as form as energy
- methaemoglobinemia: a blood disorder in which an abnormal amount of methemoglobin is produced (greater than 1-2% of Hb is Met Hb).
- caused by: genetics or chemical exposure
how do individuals witha congenital deficiency of methaemoglobin reductase compensate for the increased methaemoglobin?
in Alaskan Inuit & Appalachia people
- These individuals may go through life with as much as half of their total haemoglobin in the form of methaemoglobin
- Compensate for the defect by making more red blood cells than normal individuals (this is known as polycythemia). Thus, the total carrying capacity of the blood is increased
how does 2,3 DPG (2,3- di phosphoglycerate) help oxygen unloading occur in Hb?
2,3 DPG (2,3- di phosphoglycerate) is a small separate molecule bound loosely to the Hb molecule. When beta subunits start to deoxygenate, 2,3 DPG binds the beta subunits more tightly, moves into the centre of the Haemoglobin and increases the rate of oxygen release.
2,3 DPG (2,3- di phosphoglycerate) is critical in making S shape of ox saturation curve
Thus, it enhances the ability of RBC’s to release oxygen in hypoxic tissues.
what is percentage saturation?
how do u measure?
what should healthy individuals oxygen saturation be?
what is Sa02?
percentage saturation = the proportion of haemoglobin that is bound to oxygen
measure using a pulse oximeter
Healthy individuals at sea level should usually show oxygen saturation values between 96 and 99%, and should be above 94
sa02 = oxygen saturation
describe the shape of the oxygen / haemoglobin dissociation curve
- *- sigmoid shape
- **flat at high p02
- steep at medium and low Po2.
what if effect of temp on oxygen/haemoglobin dissociation curve?
what is Bohr shift?
Heavily metabolising tissue heats up.
Slowly metabolising tissue is colder than normal.
Heat moves the Hb curve to the right, thus unloading more oxygen at any given partial pressure. Cold moves it sharply to the left. unloading less oxygen at any given partial pressure
(A cold limb may become hypoxic and feel fatigued even if well perfused)
- *Bohr shift:**
- Heavily metabolising tissue generates more C02, and thus becomes more acidic
- Lower Ph also moves the curve to the right, the effects of heat and acid are additive. T
what is myoglobin?
how is it different to Hb? - what happens when blood passes through muscle capillaries?
what does myoglobin act as?
Myoglobin (Mb) is a form of haemoglobin that is found in muscle.
It is a single subunit, whereas normal HbA has 4 subunits.
It has a greater affinity for oxygen than Haemoglobin, therefore O2 is transferred to Mb02 as blood passes through muscle capillaries.
Mb thus forms a ‘buffer store’ of oxygen in muscle: when exercising, muscles use more o2 than local capillaries can deliver it. lag of few seconds. in those first few seconds: oxymyoglobin delivers 02.
