MEH - Anaemias Flashcards
What are the micro/normo/macrocytic anaemias?
TAILS - micro - thalassemia, anaemia of chronic disease, iron deficiency, lead poisoning, sideroblastic
ABCD - acute blood loss, bone marrow failure (aplastic or infiltrated), chronic disease, destruction (haemolysis)
FATRBCC - fetus (pregnancy), alcohol (folate deficiency), Thyroid (hypo), reticulocytosis (things causing increased reticulocyte), b12/folate deficiency, cirrhosis (liver disease), Chronic disease
Can anaemia of chronic disease be micro normo and macro?
Yes
What is a differential for Iron deficient anaemia as they present quite similarly? What are the similarities
Thalassemia
Both microcytic
Both show target cells
Both show hypochromasia
How do you test for iron deficient anaemia? What are the problems with the tests?
Serum ferritin - but also is an Acute phase protein so increased in inflammation etc so normal or increased ferritin levels don’t necessarily exclude iron deficiency
CHR - Reticulocyte haemoglobin content - but this is also reduced in thalassemia so can’t be used to differentiate
What are symptoms/signs of anaemia?
Tiredness
Shortness of breath
Palpitations
Angina
Tachycardia Pallor Angula stomatitis Spooning of nails Shiny tongue
What would you see on a blood smear in iron deficient anaemia?
Hypochromasia
Target cells
Anisopoikilocytosis (change in size and shape)
Pencil cells
What would you expect the blood results to be for iron deficient anaemia (6)?
Low Hb
Low serum ferritin
Low CHR (reticulocyte haemoglobin content)
Increased TIBC (Total iron binding capacity)
Low serum iron
Low % transferrin saturation
What does TIBC measure?
Bloods capacity to bind iron with transferrin
What does % transferrin saturation measure?
Measures the amount of iron reversibly bound to transferrin (a protein that binds to iron and transports it into cells e.g. into duodenal cells in absorption and into RBCs to transport iron into them).
Less iron less attaches so less % saturation
What is a normal MCV?
80-100
What kinds of things cause haemolytic anaemia (11)?
Sickle cell - due to misshapen and aggregates - break in capillaries
Damaged/prosthetic heart valves - shearing
Myelodysplastic disorders/ leukaemia/lymphoma ?due to autoimmune response?
Pyruvate kinase deficiency
G6PDH deficiency
DIC - due to infection/sepsis
Thalassemia
Hereditary spherocytosis
Autoimmune haemolytic anaemia
Non immune - burns
Osmotic haemolysis - drowning
What is hereditary spherocytosis?
Only produce spherocytes - get haemolytic anaemia
What happens in bone marrow failure? How do you diagnose this kind of normocytic anaemia?
Can be aplastic - not producing any RBCs due to multiple myoloma/leukaemia/lymphoma/ drugs/ post viral aplastic
Diagnose with bone marrow biopsy
What would see on a blood film with Folate/Vit B12 deficiency? Are the distinguishable? When might you see this kind of anaemia?
Megaloblastic - macrocytic
Large cells with arrest of nuclear maturation - large nucleus
Hyper segmented neutrophils
What is extra medullary haemopoiesis and when might you see it?
Not bone marrow
So liver or spleen taking over role of blood cell production e.g. in Thalassemia
Why does folate/B12 deficiency cause megaloblastic cells with large nuclei?
As it inhibits DNA synthesis so cells don’t produce enough DNA to divide at the right time and therefore grow too large with large nuclei
What is the mechanism of anaemia of chronic disease?
Functional lack of iron
Iron not released from macrophages
Reduced RBC made
How can kidney disease cause anaemia?
Decreased Epo less synthesis
How does pyruvate kinase deficiency cause anaemia?
RBC can’t complete glycolysis so no ATP is being made –> haemolytic anaemia - normocytic
What can cause folate deficiency?
Lots of things Alcohol Pregnancy Reduced in diet Some drugs - e.g. Crohns drugs methotrexate Coeliac Urinary loss in liver disease
What effect does haemolysis of RBC have on Hb in blood?
excess- haemoglobinaemia due to the breakdown of RBC releasing Hb
also increased Bilirubin
What can increased bilirubin in haemolytic anaemia lead to (2)?
Jaundice
Gallstones
What is pernicious anaemia? How does it occur?
Type of Vit B12 deficiency that is due to lack of intrinsic factor that is needed for Vit B12 absorption
Why can’t you treat pernicious anaemia with oral Vit B12? How do you treat it?
Because can’t absorb it
Need to give IM Vit B12
What are the most common causes of anaemia in pregnancy?
Iron
Folate
What is sideroblastic anaemia?
Bone marrow produces sideroblasts instead of healthy RBCs can’t incorporate boy iron into Hb
Can be apart of myelodysplastic syndrome
What might you see on a blood test that indicates anaemia of chronic disease? How do you treat it?
Increased ferritin - as storing iron lack of functional iron
Increased CRP due to disease?
Treat underlying cause
How do you treat anaemia caused by myelodysplastic syndromes?
Usually transfusions
Also chemo and stem cell transplant
Which type of anaemia do you also get neuro symptoms?
Vit B12 get focal demyelination and depression/dementia
Why is folate deficiency dangerous in pregnancy?
Neural tube defects
What do you give as treatment for chronic kidney disease anaemia?
Epo
Why can’t someone with an enzyme deficiency e.g. G6PDH have certain drugs?
Due to some drugs e.g. antibiotics having a haemolytic effect
Why might anaemia develop (think broad concepts)
RBC synthesis problem Hb synthesis problem Problem with excessive RBC breakdown Cell structure problem Enzyme/metabolism problems
What conditions might you see anaemia of chronic disease?
Rheumatoid arthritis Systemic Lupus Erythematosus Inflammatory bowel disease (UC/Crohns) TB Bronchiectasis
What might you suspect if blood marrow shows a lack of response to erythropoietin (3)?
Either empty bone marrow - e.g. after chemo/toxic insult
Infiltrated with cancer e.g. leukaemia so lack of RBC production despite Epo
Anaemia of chronic disease
What is the basis of anaemia of chronic disease?
Massive increase in IL-6 and therefore hepcidin stimulated –> lack of functional iron as less absorbed and less released from macrophages for use
What is the relevance of increased CRP in anaemia of chronic disease?
?because inflammation and infection increase CRP and also increase hecepdin
How can you tell if a bone marrow is working overdrive on histology?
Should be 50:50 fat/cells but if way more cells something going on
What 2 things are B12 and folate needed for in DNA synthesis?
Nucelar divisions and nuclear maturation
Lags behind cytoplasm so leads to big cells big nucleus open chromatin
Where is iron absorbed in the gut, where is folate absorbed and where is vic B12 absorbed?
Iron - duodenum
Vit B12 - ileum
Folate - duodenum and jejunum
How is B12 transported in blood? How is vitB12 absorbed in intestine?
Transcobalamin
Intrinsic factor
Vit B12 deficiency could result from (4):
1) Poor diet
2) No Intrinsic factor
3) Problem with transcobalamin (can be genetic)
4) Problems with ileum absorption e.g. crohns, ileal resection
What is dietary folate converted into?
Methyl THF
What can severe anaemia from vitb12 or folate deficiency lead to?
Pancytopenia i.e. low platelets and neutrophils too
What is the genetics of sickle cell?
Point mutation valine –> glutamate in position 6 on the beta chain.
Sicking disorder heterozygous
Severe sickle cell homozygous
What effect does extra medullary haematopoiesis have on spleen and liver?
Hepato and splenomegaly
What does deletion of all four alpha genes lead to in thalassemia?
Hydrops fetalis
What is a red blood cell with ‘mouth’ and pale called?
Stomatocyte
What is it called if red blood cells are all different shapes and sizes?
Polypoikilocytosis
What is it when RBC are cigar shaped?
Elliptocytes
What is it when RBC are spherical?
Spherocytes
What is it when RBC are spikey?
Acanthocytes
What happens in autoimmune haemolytic anaemia? What are the two types? What is the relevance of temperature?
Temp is when the antibody is most active
Warm immune - IgG - 37 degrees
Cold immune - IgM - 4 degrees
How might you get tear drop shaped RBCs?
Myelofibrosis - fibrous of bone marrow - little space - RBC have to squeeze out giving the tear drop shape
Why are red blood cells susceptive to oxidative stress? How do they overcome this?
Because they are oxygen carrying to exposed to radicals via this and also subjected to foreign substances in the blood that can cause oxidative stress.
Use pentose phosphate pathway to generate NADPH that is used to regenerate glutathione - glutathione donates electrons to reactive oxygen species to prevent them causing damage
What are the body’s adaptations to anaemia?
Haemopoeisis - reticulocytes
2,3BPG formation - better use of Hb - favours O2 release at tissues
CVS - vasoconstriction and tachycardia, blood redistribution away from skin and to important areas
Why does iron deficiency especially affect epithelial cells?
Because they have a high turn over and require iron
Need it for cytochrome C
Why shouldn’t you have gaviscon with oral iron supplements in anaemia?
Reduces absorption of iron
Chelator
Someone with rheumatoid arthritis and anaemia of chronic disease has low Hb but normal iron studies (ferritin etc) and high CRP - explain why
Iron studies are normal because iron still there but has been sequestered in stores - lack of functional iron
CRP due to inflammation of rheumatoid - this causes cytokine release - that acts to release hepcidin and this 1) prevents iron absorption from gut 2) Prevents release of iron from stores
Why is serum iron level not a reliable measure of iron deficiency or overload? What is?
As is is subject to diurnal variation and also reduced in ACD
Use transferrin saturation for overload - haemochromatosis
Use ferritin and CHR in iron deficiency
What is the mode of inheritance of spherocytosis?
Autosomal dominant but autosomal recessive in 25% of cases
How do spherocytes haemolyse? Can they provide enough oxygen for tissues?
Display osmotic fragility so more prone to lysis
Can do function of RBC and oxygen so that isn’t a problem
What is the main surgical management of severe heredity spherocytosis?
Splenectomy
Why can people with HS get low platelets?
Due to splenomegaly - so it pools platelets
What are some causes of increased lymphocytes (and also increased size - means they’re activated)?
Virus EBV Leukaemia Lymphoma Infectious mononucleosis
