Red Blood Cells Flashcards
what is the difference between sickle haemoglobin and normal haemoglobin?
glutamate 6 in the beta chain is mutated to valine which is hydrophobic rather than hydrophilic
structure of haemoglobin
quarternary protein made from 4 protein chains, 2 alpha and 2 beta
contain 4 harm groups (fe2+) which binds to oxygen
where do all blood cells originate from?
HSCs (haematopoietc stem cells) in the bone marrow
which cells do HSCs give rise to?
HSCs give rise to common myeloid progenitor and common lymphoid progenitor cells
haemopoiesis?
formation and development of red blood cells
typical lifespan of rbc?
120 days
two key abilities of HSCs?
self-renewal - pool of HSCs is not depleted as some daughter cells remain as HSCs
ability to differentiate into mature progeny
common myeloid progenitor?
pluripotent cell type which gives rise to erythrocytes, monocytes and granulocytes
common lymphoid progenitor?
gives rise to NK cells, T lymphocytes and B lymphocytes
sites of haemopoiesis in human lifecycle?
initially at 3 weeks in yolk sac (mesoderm)
at 6-8wks gestation liver takes over and is principal source of blood until shortly before birth
children = bone marrow and this can occur in all bones
by the time we become adults, this is limited to a few bones, mainly pelvis, femur and sternum
when does the bone marrow develop haematopoietic activity?
around 10 wks gestation
where are HSCs and progenitor cells distributed?
ordered fashion among the bone marrow amongst mesenchymal cells, endothelial cells and vasculature
what are haematopoietic growth factors?
glycoprotein hormones which bind to cell-surface receptors
growth factor for erythropoiesis and where is it made?
erythropoietin, made in kidney
growth factors for granulocyte and monocyte production?
G-CSF and G-M CSF
growth factors for platelet production?
thrombopoietin
stages of rbc development?
common myeloid progenitor –> proerythroblast –> erythroblast —> erythrocyte
young RBCs?
polychromatic, have a bluish tinge due to high RNA content
this is linked to reticulocytes which is the name given to these young RBCs
what is needed for erythropoiesis?
iron, folate, vitamin B12, erythropoietin
what does low B12/folic acid cause?
macrocytic anaemia, RBCs are large in size
= megaloblastic anaemia
what do low iron levels lead to? how is this caused?
microcytic anaemia (smaller cells)
also tend to be pale (central pallor is greater than 1/3) so are called hypochromic
caused by anaemia of chronic disease, thalassemia
erythropoietin?
glycoprotein that is synthesised in response to hypoxia, stimulates bone marrow to produce more red blood cells
major functions of iron?
transports oxygen in haemoglobin
formation of mitochondrial proteins, namely cytochrome a, b and c
forms of iron? which is better?
ham = ferrous = fe2+ (animal-derived)
non-harm = ferric = fe3+
ferrous form is better because it’s more easily absorbed by body
ferric form requires action of reducing substances
name a source of non-haem iron?
soya beans, contain phytates which further reduces absorption
problem with excess iron consumption?
toxic to organs e.g. heart and liver and therefore is tightly-controlled
how much iron absorbed per day?
1-2 mg per day
what regulates iron stores?
hepcidin, secreted by liver in response to high-storage iron
what are vitamin B12 and folate needed for?
for dTTP synthesis, this is necessary for thymidine synthesis
deficiency of either inhibits DNA synthesis
how does vitamin B12 and folate deficiency affect rapidly dividing cells?
bone marrow - cells can grow but are unable to divide properly
where is folic acid absorbed?
small intestine
when do the requirements of folic acid increase?
pregnancy
sickle cell anaemia
how is vitamin B12 absorbed?
B12 combines with intrinsic factor in (made in gastric parietal cells) stomach to form B12-IF
the B12 is first cleaved by HCl in the stomach
in the small intestine, B12-IF binds to receptors in the ileum (this is how B12 is absorbed)
causes of vitamin-B12 deficiency?
inadequate intake - veganism
inadequate secretion of IF (pernicious anaemia)
lack of acid in stomach
rbc destruction?
= after typical lifestyle of 120 days
the rbc is destroyed by the phagocytic cells of the spleen (macrophages)
most of RBC is recycled, iron from haem group returns to bone marrow where it is recycled
three things erythrocyte function depends on?
-integrity of membrane
-haemoglobin structure and function
-cellular metabolism
red blood cell membrane?
biconcave shape - aiding manoeuvrability through small red blood vessels
made up of lipid bilayer supported by protein cytoskeleton and contains transmembrane proteins
these maintain integrity of cell
disruption of vertical linkages in membrane?
hereditary spherocytosis
these are cells that are spherical in shape
lack central pallor
results from a loss of cell membrane without loss of equivalent amount of cytoplasm, so cell is forced to round up
rbcs become less flexible and are forced to haemolyse by the spleen
disruption of horizontal linkages?
= elliptocytes
these may also occur in iron deficiency
G6PD?
important enzyme in HMP shunt
HMP shunt is tightly coupled to glutathione metabolism, which protects red blood cells from oxidant damage
e.g. of oxidant = broad beans or drugs
G6PD deficiency?
x-linked inheritance, affected individuals are usually males
signs are irregularly contracted (bite) cells
polycythaemia?
too many red blood cells in circulation
Hb, RBC and Hct are all elevated
types of polycythaemia?
pseudo = reduced plasma volume
true = increase in total volume of red cells in circulation
can be caused by doping, appropriately increased erythropoietin (e.g. when at high altitudes, hypoxia)
or independent of erythropoietin (polycythaemia vera)
