Red Blood Cells

Question 1

what is the difference between sickle haemoglobin and normal haemoglobin?

Answer 1

glutamate 6 in the beta chain is mutated to valine which is hydrophobic rather than hydrophilic

Question 2

structure of haemoglobin

Answer 2

quarternary protein made from 4 protein chains, 2 alpha and 2 beta
contain 4 harm groups (fe2+) which binds to oxygen

Question 3

where do all blood cells originate from?

Answer 3

HSCs (haematopoietc stem cells) in the bone marrow

Question 4

which cells do HSCs give rise to?

Answer 4

HSCs give rise to common myeloid progenitor and common lymphoid progenitor cells

Question 5

haemopoiesis?

Answer 5

formation and development of red blood cells

Question 6

typical lifespan of rbc?

Answer 6

120 days

Question 7

two key abilities of HSCs?

Answer 7

self-renewal - pool of HSCs is not depleted as some daughter cells remain as HSCs

ability to differentiate into mature progeny

Question 8

common myeloid progenitor?

Answer 8

pluripotent cell type which gives rise to erythrocytes, monocytes and granulocytes

Question 9

common lymphoid progenitor?

Answer 9

gives rise to NK cells, T lymphocytes and B lymphocytes

Question 10

sites of haemopoiesis in human lifecycle?

Answer 10

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

Question 11

when does the bone marrow develop haematopoietic activity?

Answer 11

around 10 wks gestation

Question 12

where are HSCs and progenitor cells distributed?

Answer 12

ordered fashion among the bone marrow amongst mesenchymal cells, endothelial cells and vasculature

Question 13

what are haematopoietic growth factors?

Answer 13

glycoprotein hormones which bind to cell-surface receptors

Question 14

growth factor for erythropoiesis and where is it made?

Answer 14

erythropoietin, made in kidney

Question 15

growth factors for granulocyte and monocyte production?

Answer 15

G-CSF and G-M CSF

Question 16

growth factors for platelet production?

Answer 16

thrombopoietin

Question 17

stages of rbc development?

Answer 17

common myeloid progenitor –> proerythroblast –> erythroblast —> erythrocyte

Question 18

young RBCs?

Answer 18

polychromatic, have a bluish tinge due to high RNA content
this is linked to reticulocytes which is the name given to these young RBCs

Question 19

what is needed for erythropoiesis?

Answer 19

iron, folate, vitamin B12, erythropoietin

Question 20

what does low B12/folic acid cause?

Answer 20

macrocytic anaemia, RBCs are large in size
= megaloblastic anaemia

Question 21

what do low iron levels lead to? how is this caused?

Answer 21

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

Question 22

erythropoietin?

Answer 22

glycoprotein that is synthesised in response to hypoxia, stimulates bone marrow to produce more red blood cells

Question 23

major functions of iron?

Answer 23

transports oxygen in haemoglobin

formation of mitochondrial proteins, namely cytochrome a, b and c

Question 24

forms of iron? which is better?

Answer 24

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

Question 25

name a source of non-haem iron?

Answer 25

soya beans, contain phytates which further reduces absorption

Question 26

problem with excess iron consumption?

Answer 26

toxic to organs e.g. heart and liver and therefore is tightly-controlled

Question 27

how much iron absorbed per day?

Answer 27

1-2 mg per day

Question 28

what regulates iron stores?

Answer 28

hepcidin, secreted by liver in response to high-storage iron

Question 29

what are vitamin B12 and folate needed for?

Answer 29

for dTTP synthesis, this is necessary for thymidine synthesis deficiency of either inhibits DNA synthesis

Question 30

how does vitamin B12 and folate deficiency affect rapidly dividing cells?

Answer 30

bone marrow - cells can grow but are unable to divide properly

Question 31

where is folic acid absorbed?

Answer 31

small intestine

Question 32

when do the requirements of folic acid increase?

Answer 32

pregnancy sickle cell anaemia

Question 33

how is vitamin B12 absorbed?

Answer 33

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)

Question 34

causes of vitamin-B12 deficiency?

Answer 34

inadequate intake - veganism inadequate secretion of IF (pernicious anaemia) lack of acid in stomach

Question 35

rbc destruction?

Answer 35

= 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

Question 36

three things erythrocyte function depends on?

Answer 36

-integrity of membrane -haemoglobin structure and function -cellular metabolism

Question 37

red blood cell membrane?

Answer 37

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

Question 38

disruption of vertical linkages in membrane?

Answer 38

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

Question 39

disruption of horizontal linkages?

Answer 39

= elliptocytes these may also occur in iron deficiency

Question 40

G6PD?

Answer 40

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

Question 41

G6PD deficiency?

Answer 41

x-linked inheritance, affected individuals are usually males signs are irregularly contracted (bite) cells

Question 42

polycythaemia?

Answer 42

too many red blood cells in circulation Hb, RBC and Hct are all elevated

Question 43

types of polycythaemia?

Answer 43

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)