RBCs And Anaemia Flashcards
(84 cards)
1
Q
Where does eyrthropoesis take place before and after birth?
A
before: liver
after: bone marrow (pelvis, sternum, skull, ribs, vertebrea)
2
Q
What hormone stimulates erythropoesis, when and where is it produced?
A
- erythropoetin (EPO)
- from kidneys
- When O2 levels in blood is low
3
Q
Describe the process of erythrocyte production
A
- GATA1 and FOG1 expressed in myeloid progenitor cells commit them to erythroid progenitor cell line
- when hypoxia, EPO produced from kidneys
- EPO inhibits apoptosis of colony forming units of erythroid cell line (CFU- E)
- the erythroblasts extrude nucleus and most organelles as they develop to form reticulocytes which are released in to the circulation
- reticulocytes extrude mitochondria and ribosomes over next 1-2 days and so become erythrocytes
4
Q
What can be used as a good marker of amount of erythropoesis?
A
- EPO
- reticulocytes
5
Q
How does an RBC get its concave and flexible membrane?
A
- spectrin, ankyrin, band 4 and protein 4.2 vertically interact with the cytoskeleton
- band 3 goes across membrane
- protein 4.2 binds band 3 and ankyrin
- ankyrin binds to spectrin which acts to scaffold the actin cytoskeleton to the membrane
6
Q
What is normal blood Hb levels and what % of a RBC should be taken up by Hb?
A
130-180 g/L (male), 115-165 (female) and lower of younger ppl
95%
7
Q
How long will a RBC live in circulation for?
A
120 days
8
Q
How do RBCs produce energy if they have no mitochondria?
A
pentose- phosphate pathway
glycolysis
9
Q
What system controls eythryocyte death?
A
Reticuloendothelial system
10
Q
Where is the reticuloendothilial system? What is it mainly made up of?
A
A network of cells located throughout body- main center is in spleen/ liver though.
Made up of types of macrophages- kupffer cells in liver, langerhans in skin
11
Q
Describe the process of erythrocyte removal in spleen and haem catabolism
A
- spleen filters blood
- removes damaged erythrocytes
- sensecent RBCs have their globin removed and metabolised to amino acids
- The Hb is converted to bilirubin, which is conjugated with sugar in the liver, and removed as bile
- bacteria in the colon metabolise and deconjugate the bilirubin to urobillinogen and then to urobillin and stercobillin which is secreted and gives poo a brown colour
- urobillinogen may be reabsorbed but its secreted in urine
12
Q
What is the normal mean cell volume?
A
80-100 fL
13
Q
What is iron needed for?
A
- enzymes
- proteins
- hb
- ETC
- protection against oxidative stress
14
Q
How much iron is lost each day and due to what?
A
1-2 mg due to bleeding, hair removal, skin loss ect
15
Q
How is iron excreted?
A
there is no mechanism for iron excretion
16
Q
Where is excess iron stored and in what form? (non functional iron)
A
ferritin in liver, bone marrow, spleen, epethilial cells
haemosiderin (insoluable, in macrophages)
17
Q
What is the difference between iron from meats and iron from pulses, nuts and grain?
A
- from meats it is heam iron- mainly in ferrous state (Fe2+) so can be absorbed directly
- From nuts ect it is non heam and so mainly in the ferric state ( Fe3+) so first must be reduced to Fe2+ before absorbtion
18
Q
Describe the location and process of iron absorbtion
A
- in duodenum and upper jejnuem
- iron enters epethilial cells through the DMT1, it is either stored as ferritin or transported into blood (as ferritin)
- ferroportin is responsible for moving ferritin into blood where it binds to a carrier to become transferrin
19
Q
What is the possible fate of transferrin in the blood?
A
- taken up into bone marrow for erythropoesis
- taken up by macrophages in tissues and stored
- transferin receptor needed for transferrin absorbtion into a cell
20
Q
How is ferritin release from epithelia and macrophages regulated?
A
- hepcidin from liver inhibits ferroportin on macrophages and epithilia to increase storage (as it cant leave the cell)
- hepcidin release depends on dietary factors (sensed by villi of epethillia), body stores and erythropoesis rate
21
Q
What enhances and decreases absorption of iron?
A
- acids enhance absorption
- tea and coffee decreases absorption
- DMT expression controlled by hepcidin
22
Q
Where does most active iron come from?
A
80% from recycling within body, only 20% from absorbtion
23
Q
What can cause iron deficiency?
A
- decrease absorbtion/ intake
- veggies, diarrhoea, gaviscon reduces uptake - increased use
- physiological: pregnancy, mensuration, aspirin, growth
- pathological: bleeding (can be due to use of non- steroidal anti inflammatory drugs)
24
Q
What are symptoms of anaemia caused by iron deficiency?
A
- tiredness
- exerisize intolerance
- angina
- paleness
25
what are the signs of anaemia caused by iron deficiency?
- tachycardic
- high resp rate
- paleness
- enlarged and shiney tongue
- spoon nails
- ulcers at corners of mouth
26
What will show up on the blood test and blood film results of someone with iron deficiency
- Low Hb content (hypochromic)
- low MCV (microcytic)
- change in size and shape of RBCs (ansiopoikilocytosis)
- presence of pencil and target cells
- low serum ferritin, low serum iron and %transferritin saturation
- low reticulocyte Hb content
27
What tests can be used to diagnose iron deficiency and what are their limitations
1. can test serum ferritin
- but this is an acute phase protein so while low ferritin means definatly iron deficient, normal or high ferritin does not exclude iron deficiency
2. CHR (reticulocytes haemoglobin content)
- when low they are definatly iron deficient and wont increase unless iron goes up
- however its also low in pts with thalasaemia
28
How is iron deficiency treated?
- dietary adivce- meats, seafoods, dark leafy greens (spinach), beans ect
- IV/ IM injectons (only when severe as dangerous for heart)
- oral supplements (cause constipation and diarrhoea tho)
29
What is the result of excess iron?
- haemochromatosis
- iron is deposited in liver, pancreas, gonads, heart, skin
- leads to cirrhosis, adrenal insufficiency, heart failure, arthritis, diabetes, bronze skin
30
How can excess iron absorbtion occur?
- heredeitary (haemochromatosis), HFE gene mutation, decreased HFE, HFE normally competes with transferritin for transferrin receptor, so less HFE means more transferrin absorbed
- too many transfusions (eg in thallassaemia) mean iron builds up as its rarely lost
31
How ca hereditary haemochromatosis be treated?
- draining blood (phlebotomy)
32
How can transfusion associated haemochromatosis be prevented?
- iron chelating agents delay the effects of iron overload
33
Why might anaemia develop?
- reduced/ ineffective erythropoesis
- problems with Hb synthesis
- loss of RBCs from circulation
- problems with RBC membrane and metabolism
- folate/ b12 deficiency
- increased RBC removal
34
What is anaemia?
- A low Hb concentration
35
What are the symptoms for slow and acute onset anaemia?
slow onset: may be asymptomatic as body adjusts- decreased BPG, increased HR, EPO release ect
acute onset: headaches, pallor, fatigue, short of breath, angina
36
What can cause deficancies in RBC production?
Radiation, chemicals (benzene), chemotherapy, parovirus
All these mean bone marrow not respond to EPO.
Or deficiencies in feed back look that creates EPO: kidney disease
37
What else on a blood result suggests anaemia is due to reduced red cell production?
- aplastic anaemia (low WBCs, platelets ect)
| - low reticulocytes
38
What type of anaemia is caused by iron deficiancy?
microcytic
39
What type of anaemia is anaemia of chronic disease?
microcytic
40
Describe the pathophysiology of anaemia of chronic disease?
- chronic inflammatory diseases (RA, TB, malignancies ect) mean more activity of macrophages
- this means shorter RBC life span
- and cytokines like Il6 increase hepcidin release so more iron stored
- also decreases sensitivity of bone marrow to EPO
41
What will reticulocyte count, CRP and levels be in anaemia of chronic disease?
reticulocyte normal
CRP high
Ferritin high
42
Is thalasamia micro, normo or macrocytic?
microcytic
43
What is thallasaemia B major?
Both beta- globin chains are defective/ missing- ver severe
44
What is thalassaemia B minor?
When only on beta- globin chain is defective/ missing
45
What is thalassemia B intermida?
one beta globin gene missing on each chromosome
46
Is someone is only misssing one alpha globin gene will they present with symptoms?
no
47
What is HbH disease?
3 alpha globin genes are missing, tetramers of Beta globin form (HbH) this is moderately severe anaemia and makes microcytic RBCs
48
What is hydrops fetalis?
all 4 alpha globin genes missing
| y tetramers in foetus not sufficient so foetus dies
49
If anaemia is due to loss of red cells (bleeding) what will be the MCV?
microcytic
50
What can cause chronic excessive bleeding?
- gastric ulcers
- gastric cancer
- colon cancer
- menorrhagia
- using NSAID such as ibuprofen cause GI bleeding
51
Name some inherited problems of RBC membranes
- spherocytosis (RBCs become spherical)
- Elliptocytosis (RBCs take cigar shape)
- Pyropoikliocytosis
- stomatocytosis (swell and burst as cant hold Na and K well)
52
What is the inheritance pattern of herediatry spherocytosis?
auto dominant
53
What are the signs of herediary spherocytosis?
- haemolytic anaemia
- jaundice
- spelnomegaly
- gall stones
- many ppl asymptomatic
54
What will be the blood test and film results of hereditary spherocytosis? How is it diagnosed?
- Hb low
- platelets low- they pool in the spleen
- MCV normal - more reticulocytes and these are larger so will counteract the fact that defctive blood cells are small
- Reticulocytes high- compensation
- blood film shows spherical RBCs
- the EMA binding test will be abnormal
55
What can cause aquired problems with RBC membranes?
- mechanical damage- heart valves, vasculitis, MAHA, DIC
- Heat damage (burns)
- osmotic damage (downing)
56
What two metabolic disorders cause anaemia?
- G6PHD deficiency
| - Pyruvate kinase deficiency
57
Why does G6PHD deficiency cause anaemia?
- Needed for pentose phosphate pathway
- This is needed for NADPH production
- Which is needed for glutathoine reduction
- This needed to protect against oxidative damage
- So leads to haemolytic anaemia
58
Why does pyruvate kinase deficiency lead to anaemia?
- needed for final step of glycolysis to create ATP
- This is the only way RBCs can produce energy (no mitochondria)
- cant fuel Na/ K pump
- Cell shrinks and dies
59
What other hereditary condition causes abnormal Hb synthesis?
sickle cell disease
60
Why do you get hepatosplenomegaly and bone expansion in thalassaemia?
- They try to compensate for anaemia so enlarge as they increase blood cell production
61
Why do ppl with thalassaemia often get iron overload?
- lots of transfusions is part of their treatment
| - excessive absorption of iron due to ineffective haematopoesis
62
What can cause excess removal of RBCs?
- autoimmune conditions
- antibodies bind to RBCs, so theyre destroyed in spleen
- increased reticulocytes to compensate, raised billirubin (more heam breakdown), raides LDH (RBCs rich in this enzyme)
63
What enzyme can be tested for in the blood and suggests haemolytic anaemia?
LDH
64
How does the MCV change in anaemia due to B12 or folate deficiency and why ?
It becomes macrocytic (>100fL)
| They're both needed for DNA synthesis, so the cytoplasm development is faster than cell division and nuclear maturation
65
What is the role of folate ?
- acceptor of a single carbon from amino acids, which can go on to provide the carbon for other compounds (creates the one carbon pool)
- The one carbon pool is needed for purine base synthesis and transfer of methyl on to B12
- Role prominent in RBC precursor cells
66
What happens to folate once it is absorbed?
- absorbed by proximal intestine
- converted to methyl tetrahydrofolate
- taken to liver
- stored
67
What foods is folate present in?
liver, leafy greens
68
Other than dietary insufficiency, what can cause folate deficiency?
pregnancy, severe skin diseases (psoriasis), ALCOHOLISM (damages intestine), proximal small bowel diseases (crohns, coeliac), anticovulsant drugs, liver disease, heart failure
69
Where is B12 obtained from?
eating animal based foods, its originally synthesised by microorganisms
70
Describe what happens B12 after ingestion
- B12 binds to hepatocorrins- this complex is digested by pancreatic proteases to release the B12
- this is combined with intrinsic factor (IF) produced by partietal cells in stomach
- Binds to illeum, B12 absorbed, IF destroyed
- B12 bound to transcobalamin which delivers it to bone marrow and other tissues
71
What can cause B12 deficiency?
- vegetarian diet- most from animal foods
- Auto immune destruction of parietal cells
- gastroectomy
- diseases of ileum (crohns ect)
- congenital defiencies in transcoalbumin
72
How does B12 deficiency lead to functional folate deficiency?
- B12 is needed to remove a methyl group from methyl tetrahydrofolate and put it on a methionine
- folate therefor not available for purine synthesis
73
How long can you last without eating B12 before you become symptomatic?
years because it is in large surpless in the body
74
What other effect is there to B12 deficiency but not folate?
- focal demyelination of some nerves
| - leads to depression and dementia
75
What 3 major processes can cause polycytheamia (High RBC conc)?
- myeloproliferative disorders (eg polycythemia vera)
- EPO receptor mutation so always active
- a physiological reaction
- reaction to secondary condition (smoking ect)
- dehydration leads to low plasma vol so relative polycythaemia
76
What is the cause of most myeloproliferative disorders?
usually mutations to JAK2 genes, meaning over activity of progenitor cells
77
What are the key clinical features of polycythaemia vera?
- Pruritis (itching) often after hot shower- unknown cause
- splenomegaly leads to fullness and abdo discomfort (more RBC destruction)
- tiredness, muscle aches- more viscous blood
- headaches, confusion, dizziness- more viscous blood = less to brain
- increased bleeding (gums) and high risk of thrombus - mutation often also affects platelet formation
- high haematocrit and Hb
- JAK2 mutation
78
What is the difference between relative and absolute ertyhrocytosis?
relative is normal red cell mass but low plasma volume.
| Absolute is normal plasma volume and high red cell mass
79
What could lead to increased EPO (causing erytrocytosis)?
- central hypoxia (chronic lung disease, CO poising, altitude training)
- renal hypoxia (renal artery stenosis, kidney failure)
- Many cancers (renal cell cancer, hepatocellular carcinoma)
- EPO injection in cyclists
80
How is polycythaemia vera managed?
- venesection (remove blood)
- aspirin (thins blood, reduces clot risk)
- manage CVS risk factors
- other drugs can be used if splenomegaly becomes symptomatic/ disease progresses ect
81
What is the difference between primary and secondary polycythaemia?
primary is something that directly causes raised haematocrit- polycthaemia vera
secondary is heamatocrit being raised due to an increase in EPO production for example at altitude
82
What genes are expresses in myeloid cells that commits them to the erythroid lineage?
GATA1, FOG1 and PU.1
83
How does EPO work to increase erythropoesis?
inhibits apoptosis of CFU-E cells (colony forming units of the erythroid cell line)
84
What is pernicious anaemia?
lack of intrinsic factor so you cannot absorb b12
