3. red blood cells and haemoglobin Flashcards
describe the different needs for oxygen in different regions while exercising
brain and arms : active but moderate needs, so must release some oxygen here
lungs: area high in oxygen, so haemoglobin must maximally absorb oxygen here
gut: shuts down during exercise so needs little oxygen delivered
legs: working hard so area is low in oxygen and high in metabolic products. haemoglobin needs to give up lots of oxygen here
rbc: simplicity of form
biconcave shape optimises oxygen uptake and delivery
surface area maximised and diffusion distance decreased for collecting and releasing oxygen
red cell is also flexible and this allows the cell to bend and form different shapes
rbc: cytoskeleton function
red blood cell must have optimal shape to move safely through different blood vessels
flexibility eg when the legs move they bend and twist the capillaries so the red blood cell must be adaptable and move without being destroyed
optimises gas exchange , at rest is biconcave disc
structure/function of rbc
delivers o2 to tissues proportional to need
simplicity and specialised functional features leave it vulnerable to disease
some rbc genes preserved at high frequencies
benefits of simplicity of rbc
red blood cell has given up nucleus mitochondria and ribosomes
well adapted cytoskeleton and simple metabolism allows red cell to be efficient and stable, contains nothing unnecessary
room for haemoglobin as no nucleus and more space for flexibility
be unattractive to infecting organisms as most need lots of proteins and they find oxygen highly toxic
drawbacks of simplicity of rbc
rbc cant make new proteins so hard to repair itself from damage and it cant make more Hb so cant self destruct as this requires protein
no nucleus means no capacity for making mRNA
no mitochondria means no TCA cycle which limits the capacity to generate ATP or reducing power , leaving the red cell vulnerable
no ribosomes means no MRA translation which means no protein synthesis
draw cytoskeleton of rbc
vertical interactions in the membrane, containing band 3 protein with ankyrin at its base and then 4.2 joined to tht . glycophorin C is also in the membrane with 4.1 at its base and then tropomyosin joined to tht
betasporin chains below the membrane
horizontal interactions span across
red cell as flexible container - cytoskeleton
phospholipids which go through the bilayer act as anchors and hold ankyrin proteins which are involved in vertical interactions
we get vertical anchors and horizontal linkers (draw)
why is biconcave disc an optimal shape
structure provides good SA:V ratio with short diffusion distance for oxygen entry
rbc in optimal flow
rbc structure can compress into a torpedo shape in high flow or turbulence
structure can also flex to allow cells to pass through small branched vessels in tissues
the membrane and damage repair
the red blood cell cant undergo apoptosis, needs temporary fixing to prevent toxicity
red blood cells like to form chains and stick together but the rbc must be adapted to avoid that process, membrane itself is self repairing to limit immediate damage
damage limitation
rbc must not burst, if haemoglobin is released into the circulation its highly toxic
cytoskeleton is structured to prevent Hb leakage
rbc is self sealing, forms vacuole then pops itself
example of self sealing rbc
damage by fibrin strands in circulation caused by local clotting activation
slicing damage to cell
repair and vacuole formation
vacuole pops, but rbc sealed, left with bite cell
further sealed fragments may be formed
if seen with spikes on blood film indicates kidney damage
example of diffuse damage
eg from an inherited abnormal cytoskeleton or antibody which may cause diffuse membrane loss
membrane is damaged diffusely
small sealed blebs of membrane are lost
the cell shrinks gradually becoming a rigid sphere
the rigid damaged spherocyte is removed in the spleen
haemoglobin structure and function
sigmoid dissociation curve for oxygen release
oxygen is held tightly in high PaO2 and released linearly giving a sigmoid shape
describe Hb dissociation curve
y axis is oxygen bound to haemoglobin and x axis is PaO2
to the right ie the highest point in curve where high PaO2 id the lungs where there is complete uptake of O2 by Hb
then going down the curve to the middle pf the graph is the PaO2 in tissues where there is the progressive release of oxygen according to need
only haemoglobin acts this way to give a sigmoid curvem this is due to haem the oxygen binding chemical element and globin which surrounds the protein elements
haem
porphyrin structure which holds iron in a flat 2D structure
there are two interaction sites above and below the plane
one binds to globin protein and the other binds to oxygen
globin
binding of protein to globin keeps the haem contained so its not free
globin protein wraps tightly round the iron to protect it and to control the volume of oxygen
function of globin 1
if relaxed o2 can stick tightly in the middle as have lots of room for it and globin is veery able to bind haem
if globin protein is tight, oxygen binds far less strongly because the protein does not want oxygen in there
function of globin 2
to produce the sigmoid dissociation curve
eg if we only had one isolated chain we would get a hyperbolic curve where oxygen is taken up into the lung easily and passes through the starter tissues byt doesn’t give the oxygen up at all but when oxygen hits later tissues all of it is released
release of ooxygen not progressive and o2 is only fully released in tissue hypoxia which wouldn’t be good
structure of Hb
four chain four globins four irons and four oxygens
alpha beta beta alpha
four chains cooperate and link with their iron molecules in the middle and their porphyrin rings
interconnected, a change to one chain will affect the others
process of oxygen release by haemoglobin
relaxed form leaves the lungs, chains under no tension so binds four oxygen molecules . holds onto oxygen tightly until relaxed form passes through the tissues and oxygen levels drop. one oxygen molecule is released and structure and ring become tightened. the other three chains are more likely to give up their oxygen
second oxygen is released gets even tighter so next two oxygen molecules are given up more easily and readily
when one oxygen is bound the tight form gives it up quickly
other features of the globin structure
tight and relaxed structures are also affected by pH CO2 and metaboic products eg in active tissues where they promote the tight formation for better oxygen release
eg exercising legs mean acidic and metabolic prodcuts produced eg high 2,3 DPG so tight formation and lower oxygen affinity so oxygen preferentially released in tissues
physiological Hb variation during development
during development embryo and foetus make different haemoglobins
foetal haemoglobin HbF
doesn’t bind 2,3 DPG so has a higher affinity for haemoglobin so HbF can compete with mothers Hb for oxygen. transfers oxygen from mother to foetus
HbF structure of chains is different as it cant bind DPG so always has higher affinity for oxygen than the mother
the mother must also increase her red blood cell mass as theyre competing
red cell and disease
erythrocyte is vulnerable to disease as it has no natural defense
but iron rich haemoglobin is inhospitable to bacteria
the red blood cells are useless to viruses as it cant aid their reproduction (lacking biosynthetic capabilities) as it has no nucleus
malaria
plasmodium falciparum is the malarial parasite , vector is mosquito. Plasmodium can live inside rbc and be protected from the immune system whilst metabolising their haemoglobin for energy, replicating then affecting other red cells
huge evolutionary pressure that’s killed more than half the humans who ever lived
mechanism of plasmodium
vacuole has metabolic activity, metabolises Hb and grows, changing rbc structure so can fit into capillaries
they then crinkle to make channels and pores and self replicate to burst or form gametocytes which are taken up by mosquitoes
inherited red cell diseases
homozygous = mortality
heterozygous = malarial protection
eg haemoglobin S, beta thalassaemia, glucose 6 phosphate dehydrogenase G6PD, HbC
all have high gene frequencies as they offer protection
G6PD
glucose 6 phosphate dehydrogenase is a red blood cell enzyme that generates reducing power (NADPH) that protects haemoglobin from oxidative damage. red cell has simple metabolism ie only does glycolysis no TCA so depends on G6PD
deficiency provides malarial protection as cells infected by parasite are inhospitable as the oxidative stresses denature the Hb and less is available fir the parasite to consume
G6PD deficiency
when oxidative stress is high, reducing power is not generated so haemoglobin is damaged and shrinks to one side of the cell in denatured form .
Hb precipitates the damaged stuff, membrane goes irregular and shrinks to one side of the cell. called blister cells after infection
body responds by making more rbc but slightly blue as still has ribosomes in it. pressure released for circulation
deficiency can cause death if food or meds are ingested which increase oxidation
blister cell formed leads to cell destruction and anaemia and low Hb
sickle cell disease
arises due to single gene mutation substituting one amino acid in the beta haemoglobin chain
makes Hb stick together into long polymeric chains so rbc becomes elongated and rigid / inflexible
process happens when sickle Hb is deoxygenated (ie long chains form)
sickle cells are prematurely destroyed in the spleen
abnormal Hb confers resistance to parasite as infected cells become sickled and are prematurely destroyed in the spleen
beta thalassaemia
Beta haemoglobin chain has decreased or absent function so alpha/ beta haemoglobin molecule not fully formed. Rbcs deficient in haemoglobin
low haemoglobin environment is inhospitable to malarial parasites as don’t develop efficiently
sufferers are chronically anaemic , don’t make enough beta-haemoglobin chains and so alpha tries to form all the chains but they stick together and precipitate out
blood film - thalassaemia
cells small and pale (smaller than a lymphocyte)
severe: rbc look almost blue with thin ring of haemoglobin
