3. red blood cells and haemoglobin

Question 1

describe the different needs for oxygen in different regions while exercising

Answer 1

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

Question 2

rbc: simplicity of form

Answer 2

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

Question 3

rbc: cytoskeleton function

Answer 3

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

Question 4

structure/function of rbc

Answer 4

delivers o2 to tissues proportional to need
simplicity and specialised functional features leave it vulnerable to disease
some rbc genes preserved at high frequencies

Question 5

benefits of simplicity of rbc

Answer 5

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

Question 6

drawbacks of simplicity of rbc

Answer 6

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

Question 7

draw cytoskeleton of rbc

Answer 7

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

Question 8

red cell as flexible container - cytoskeleton

Answer 8

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)

Question 9

why is biconcave disc an optimal shape

Answer 9

structure provides good SA:V ratio with short diffusion distance for oxygen entry

Question 10

rbc in optimal flow

Answer 10

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

Question 11

the membrane and damage repair

Answer 11

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

Question 12

damage limitation

Answer 12

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

Question 13

example of self sealing rbc

Answer 13

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

Question 14

example of diffuse damage

Answer 14

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

Question 15

haemoglobin structure and function

Answer 15

sigmoid dissociation curve for oxygen release

oxygen is held tightly in high PaO2 and released linearly giving a sigmoid shape

Question 16

describe Hb dissociation curve

Answer 16

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

Question 17

haem

Answer 17

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

Question 18

globin

Answer 18

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

Question 19

function of globin 1

Answer 19

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

Question 20

function of globin 2

Answer 20

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

Question 21

structure of Hb

Answer 21

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

Question 22

process of oxygen release by haemoglobin

Answer 22

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

Question 23

other features of the globin structure

Answer 23

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

Question 24

physiological Hb variation during development

Answer 24

during development embryo and foetus make different haemoglobins

Question 25

foetal haemoglobin HbF

Answer 25

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

Question 26

red cell and disease

Answer 26

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

Question 27

malaria

Answer 27

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

Question 28

mechanism of plasmodium

Answer 28

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

Question 29

inherited red cell diseases

Answer 29

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

Question 30

G6PD

Answer 30

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

Question 31

G6PD deficiency

Answer 31

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

Question 32

sickle cell disease

Answer 32

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

Question 33

beta thalassaemia

Answer 33

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

Question 34

blood film - thalassaemia

Answer 34

cells small and pale (smaller than a lymphocyte)

severe: rbc look almost blue with thin ring of haemoglobin