Red blood cells Flashcards
how is oxygen moved in circulation
cooperativity and allosteric effect (more O2 bound in lungs and deposited in tissue)
how is oxygen carried in blood
poorly soluble in plasma - normal arterial blood flow carries 70x more O2 on haemoglobin than plasma
what is a key feature of haemoglobin binding to oxygen
must be weak enough to be reversible (mechanisms at muscles to reduce affinity)
cooperativity and right shifting of binding curve
what makes up the majority of RBCs
95% dry weight is haemoglobin
what is the structure of haemoglobin
each subunit has a ham group (616 Da) and and a large globin peptide (17000 Da)
Allosteric properties = cooperativity
what is a ham group
each haemoglobin and myoglobin has 1 ham group (carries O2)
what is the structure of a haem
porphyrin ring, rigid, 2D, highly coloured due to electron sharing
conjugated to iron ion (ferrous aka Fe2+)
how do haemoglobin’s 4 sub units interact
cooperativity
each sub unit has 1 oxygen molecule on its haem
each sub unit influences its 3 neighbours
O2 binding increases affinity leading to more binding and the same for release
what is the structure of haemoglobin
healthy adults HbA (2 a and 2 B subunits) aka maternal Hb
Foetal HbF (2 a and 2 g sub units)
adults have 1% HbF (binds to oxygen more strongly than HbA)
How does CO2 and H+ affect binding to Hb
Bohr Effect
Increased CO2 decreases affinity for oxygen (decreases blood pH via carbonic anhydrase)
CO2 and H+ bind to different parts of Hb than O2
How is CO2 transported in blood
10% dissolved
22% carbamino
68% as HCO3-
how is CO2 transported as carbamino
CO2 + Hb-NH2 <=> Hb-NH-COOH
how is CO2 transported as HCO3-
CO2 in, CO2 + H20 <=> H2CO3 <=> H+ + HCO3-, Cl- exchange (chloride shift) via band 3 protein
what is chloride shift
more chloride in venous blood than arterial
how does oxygen binding compare between myoglobin and haemoglobin
myoglobin - hyperbolic
haemoglobin - sigmoidal
what causes a rightward shift in oxygen affinity (decrease)
CO2 H+ Cl- 2,3-DPG (diphosphoglycerate) and muscle activity
how does 2,3 DPG lower oxygen affinity
binds to Hb
found in erythrocytes at 5mM
tiny molecule compared to Hb
HbF has a lower affinity than HbA so has a higher affinity for oxygen
how do oxygen saturation curves compare for material and foetal Hb
Myoglobin exponential
HbF sigmoidal (higher than HbA)
HbA sigmoidal
how does oxygen concentration vary in active muscles
O2 low, CO2 high, blood slightly acidic, temp high, myoglobin
as blood runs along capillary O2 leaves Hb, CO2 and H+ bind (RHS shift of oxygen saturation)
HCO3- leaves Plasma and Cl- enters
what is breathing controlled by
O2, CO2 and H+
plasma O2 must drop precipitously before respiration drive increases
what is the main driver to increase respiration rate
H+ in CSF (H+ in blood is slow into CSF but CO2 quicker so can make HCO3- and H+)
CO2 response same as H+ (blood based, signal from carotid arch)
what detects the increase of H+ in the CSF
medullary receptors sample from interstitial and CSF fluid
what is the structure of erythrocytes
definite/ mature
biconcave disc, red when oxygenated, anucleate, no organelles, contains Hb
what is the function of erythrocytes
bag of Hb to transport CO2 and O2
survive for 120 days
very flexible (fold and stack in blood vessels)
how many erythrocytes are there
per um of blood they are the most numerous (5 million compared to 9000 leukocytes and 7000 platelets)
what is haematocrit/ PCV
40-52% MALES and 36-48% FEMALES (amount in blood)
13-17 g/dl MALES and 12-16 g/dl FEMALES
what is the mean cell Hb (MCH)
27-34 pg
what is the mean corpuscular volume (MCV)
80-100 fL
Where does erythrogenesis occur
after birth - bone marrow only
after 20 y/o membranous bones only
in embryo - liver, spleen, lymph nodes, yolk sac
how does erythropoiesis occur
haematopoetic stem cell to burst forming unit erythroid to colony forming unit erythroid to erythroblasts to reticulocytes to erythrocytes
up to R in bone marrow
B to Eblasts is erythropoietin dependant
Eblasts to R is iron dependant
what is erythropoietin
A cytokine/ hormone to drive erythropoiesis
made in kidney (response to hypoxia)
how can erythropoietin be used medically
used to stimulate erythropoiesis (severe risks of severe target effects)
performance enhancing drugs for athletes
what are reticulocytes
RBC precursor (before complete extrusion of nucleus and organelles) 2 days in blood then definitive RBC
how can reticulocyte be used as a diagnostic tool for anaemia
indicate bone marrow activity
high in haemolytic anaemias (homeostatic response)
low when erythropoiesis is low
machine counts and detects those with low basophilic material (eg DNA) in them
what is methamoglobinaemia
Hb cannot transport O2
Fe in Hb is oxidised (Fe3+) instead of ferrous (Fe2+)
what causes methamoglobinaemia
due to congenital globin mutations (HbM), hereditary decrease of NADH, toxic substances
what causes CO poisoning
CO displaces O2 from Hb (same bind site as affinity is 250x stronger so low levels can displace more 02)
PO2 blood dissolved in blood normal
lethal
what are the symptoms of CO poisoning
bright red blood, brain affected 1st = disorientation
how is CO poisoning treated
95% oxygen/5% carbon dioxide (drives Hb to T configuration)
allows for CO to be displaced
what is polycythaemia
increase number of RBCs therefore viscosity of blood so clogs blood vessels
what are the types of polycythaemia
physiologic - high altitude
Polycythaemia vera - neoplasm, often asymptomatic, risk of thrombotic events, no cure so treat with venesection (all ages but increases with it, possibly genetic)
what is iron required for
to produce RBCs, 65% of all iron in adults is in RBC Hb
where is Fe stored
stored intracellularly as ferritin and haemosidesin (30%)
stored in reticulo endothelial system (liver, spleen, RBCs, bone marrow, macrophages and monocytes)
what causes anaemia
deplete in all stores
only a small % of dietary iron absorbed
lose 1mg a day (more in pregnancy, menstruation and peptic ulcer)
what is vitamin B12 and folic acid used for
important for rapidly dividing tissue (essential for DNA thymidine)
nuclear maturation fails (RBCs, skin, gametogenesis)
leads to fragile cells
what causes vitamin b12 and folic acid deficiency
diet, malabsorption, lack of utilisation
eg vegan, pernicious anaemia, pregnancy, haemolytic anaemia, lymphoma, old age, institutions, famine
how can vitamin b12 and folic acid deficiency be treated
with vitamins
oral folic acid or intramuscular hydroxocobalamin
what is iron deficiency
hypo chromic microcytic anaemia
cells keep dividing but cannot fill up with Hb
what is vitamin b12 and folic acid deficiency
megaloblastic anaemia
pernicious anaemia
cells keep filling up with Hb but cannot divide fast enough
