Haemopoiesis Flashcards
what are produced in the bone marrow
RBC, platelets and WBC
where is bone marrow found
throughout the skeleton in infancy but limited to the pelvis, skull, ribs, sternum and vertebrae in adults
what are the 2 types of bone marrow test
bone marrow trephine biopsy (taking a 1-2cm core of bone marrow to look at structure) or bone marrow aspiration (taking bone marrow cells to look at finer details)
what type of cells do blood cells come from
multipotent hematopoietic cells
what are hematopoietic cells differeniate into
myeloid progenitor cells or common lymphoid progenitor cells
what controls haematopoiesis
the reduced oxygen is detected by the peritubular kidney cells which then increase their production of erythropoietin which stimulates release and maturation of RBC
what cells are involved in the reticuloendotheial system
monocytes, macrophages, kupffer cells, microglial cells
what do cells in the RES system do
identify old, abnormal blood cells and phagocytose them mainly in the spleen or liver.
how long do erythrocytes live for
120 days
what are the functions of erythrocytes
- carry haemoglobin
- maintain the ferrous/reduced state of haemoglobin
- generate ATP
- maintain osmotic pressure
describe the structure of RBCs
- have proteins in their membranes making them flexible so can bend through capillaries
- large SA to vol ratio
- biconcave shape
which gene codes for the production of haemoglobin and where is it found
globin gene found on chromosomes 11 and 16
at what age do you switch from foetal to adult haemoglobin
3-6 months
what do the globin chains do
- prevent the haem molecule from oxidation, preventing the ferric form being produced from the ferrous
- allows variation in oxygen affinity by changing shape
- allow solubility
describe the break down of haemoglobin
macrophage or kupffer cells break it down into globin (a protein which is then broken down into amino acids) and heme. The irons is taken from the heme to be used. the rest of the molecule is converted to bilirubin in the liver and conjugated to be excreted
what does an excess in bilirubin result in
jaundice
why do you get anaemia with damaged kidneys
cant produce erythropoietin hormone so there is a decrease in haemoglobin production
what are the 2 main metabolic pathways in RBC
- glycolysis
- pentose phosphate pathway
what happens if metabolism is altered in RBC
their membrane changes and so they break down quicker so you become anaemic
what are the types of available iron
- in haemoglobin
- in myoglobin
- tissue iron e.g. iron used in enzymes
- serum/transported iron
what are the types of stored iron
- ferritin
- haemosiderin
what happens to iron requirement in pregnancy
increases
where does most of the active iron in our body come from
breakdown of RBC (not absorption in the gut from food)
what is 95% of iron in the liver stored as and in what cells?
what about the remaining 5%
- ferritin in hepatocytes
- the other 5% is as haemosiderin in kupffer cells
how is iron excreted from the body
its not excreted - only small amounts are lost each day by the loss of skin, hair and gut cells
how much iron enters and leaves the body in a day
1-2mg
what are the differences between haem and non-haem iron
- haem is a better source of iron found in meat which enters enterocytes (cells lining intestines) as Fe 2+ (ferrous)
- non-haem is found in pulses and grains and exists as Fe3+ (ferric)
what happens to non-haem iron in order to be taken up by enterocytes
stomach acid converts it into ferrous which then binds to transferrin which allows it to be taken up by the enterocytes in the duodenum and upper jejunum. can then be stored in the liver as ferritin or transported in the blood for use
what exports iron out of the cells
ferroportin
what is lactoferrin
primary iron source in infants
how is iron taken into cells such as RBCs
binding of iron transferrin complex to a transferrin receptor
what cells contain the highest number of transferrin receptors
RBCs
what controls iron absorption
- levels are sensed by villi of enterocytes
- can regulate transporters
- control transferrin and HFE receptor expression
- cytokines
outline the role of hepcidin
it is a negative regulator of iron absorption which works by binding to ferroportin and so stops iron leaving enterocytes or macrophages giving a build up of non-functional iron
what does an iron deficiency result from
- insufficient intake
- increased use
what are the signs and symptoms of an iron deficiency
- tiredness
- reduced oxygen carrying capacity
- cardiac symptoms
- tachycardia
- increased respiratory rate
- epithelia changes (shiny tongue and spooning of nails)
what is hypochromic iron deficiency
low haemoglobin content
what is a microcytic iron deficiency
small RBCs as the cells will carry on dividing
what is anisopoikilocytosis
change in size and shape of RBC
how can you test for an iron deficiency
- ferritin test (but this is an acute phase protein so will increase in infection)
- Recticulocyte haemoglobin content - CHR (this is low in thalasaemias)
what are the treatments to an iron deficiency
- dietary advice
- oral supplements
- intramuscular injections
- intravenous
- transfusion (but only in severe anaemia)
why is excess iron dangerous
it can produce highly reactive hydroxyl and lipid radicals which damage lipid membranes, nucleic acids and proteins. the excess iron is deposited in tissues
what is haemochromatosis
- iron excess resulting in organ damage due to deposition
- can causes liver cirrhosis, diabetes, cardiomyopathy
- can be hereditary or transfusion associated
what is hereditary haemochromatosis
an autosomal recessive disease due to mutation on the HFE gene
HFE normally competes with transferrin for binding to the transferrin receptor so without there is no competition so too much iron enters cells. treated with venesection
