Anaemia Flashcards
What is the life span of a RBC
4 months
Describe the structure of Haemoglobin
2 alpha protein chains
2 beta protein chains
Each chain has an Fe2+ and a heme group
What is anaemia
Low Hb
What are the 3 mechanisms that can result in anaemia
- Decreased production of red cells
- Increased destruction of red cells
- Loss of red cells - bleeding
What can cause the decreased production of red cells in anaemia
- iron deficiency
- B12 or folate deficiency
- Marrow infiltration e.g. cancer
- Any chronic disease e.g. rheumatoid, cancer
What classifications of anaemia are there
- Inherited or Acquired
- Microcytic, Microcytic, Normocytic
- Immune or Non-immune
How big are micro, normo and microcytic RBCs
<76fl = microcytic 76-96fl = normocytic >96fl = macrocytic
What does anaemia caused by defective Hb synthesis result in
RBCs that are small - microcytic
And contain reduced amounts of Hb - hypochromic
What factors can help to enhance iron absorption
- Haem iron (meat)
- Ferrous salts (Fe2+)
- Acid pH
- Iron deficiency
- Pregnancy
- Hypoxia
What factors impair iron absorption
- Non-haem iron (veg)
- Ferric salts (Fe3+)
- Alkaline pH
- Iron overload
- Inflammatory disorders
Describe the basic histology (or morphology? idk) of normal blood cells
- Red cells
- Uniform size
- Pale centre
Describe the basic histology (or morphology? idk) of iron deficient blood cells
- Red cells
- Variable size
- Small
- Pale
- Target cells, pencil cells
What allows you to confirm iron deficiency
- FBC
- Blood film
- Decreased serum ferritin (storage iron)
- Decreased serum iron and increased total iron binding capacity (TIBC) (not used as often now)
- Transferrin saturation (iron/TIBC x 100%) <15% iron deficiency
AY BAWS CAN I HABE DE NOTE PLZ
Iron deficiency is not a diagnosis: find the cause
What treatments are there to replace iron
Diet?
Oral iron is best
Avoid blood transfusion
What disorder does iron deficiency look like
Thalassaemia
What are the risk factors for anaemia with normal MCV
- Acute blood loss
- Chronic disease
- Cancer
- Renal disease
- Haemolysis
What are some risk factors for anaemia by marrow infiltration
- Metastatic cancers
- Myeloma
- Myelofibrosis
- Leukaemia and lymphoma
Describe the mechanism of anaemia from chronic disease
- Reduced RBC lifespan
- Poor marrow response to Epo
- Depressed erythropoiesis
- Inflammatory cytokines (e.g. IL-1, TNF-alpha) - interfere with Epo production and actions
What iron findings and Blood findings are usually found in anaemia of chronic disease
- Hb 7-11g/dL
- MCV normal
- Serum iron - low
- TIBC - low
- Ferritin - high
- Blood film - not helpful
What deficiencies are found in microcytic anaemia
Vit B12 or Folate
What is Vit B12 and folate used for and why does it lead to macrocytic RBCs
used for DNA synthesis, without it = DNA synthesis impaired and cells fail to divide = large cells
Where is vitamin B12 found
Meat, eggs, animal proteins
Where is folate found
liver, greens, yeast - destroyed by cooking
AY BAWS CAN I HABE DE NOTE PLZ
B12 and folate deficiencies look identical
What changes in biochemistry can be seen from B12 and folate deficiencies
Increased Lactate dehydrogenase
Increase bilirubin
What can cause gastric malabsorption of B12 deficiency
Pernicious anaemia
Total/partial gastrectomy
What can cause intestinal malabsorption of B12 deficiency
- Stagnant loop syndromes
- Ileal disease
- Crohn’s
- Fish tapeworm
What is pernicious anaemia, what causes it and what does it lead to
Autoimmune disorder where an autoantibody against the gastric mucosa and intrinsic factor (IF) leads to gastric atrophy, decreased acid and IF secretion
What are the clinical features of pernicious anaemia
- Insidious (fatal untreated)
- Anaemia
- Glossitis
- Mild jaundice
- Neurological: peripheral neuropathy, post and alt column damage, dementia, optic atrophy
What prescription is given to patients with pernicious anaemia
Intramuscular B12 every 3 months for life
What causes of folate deficiency are there
- Old age, poverty, alcoholism
- Coeliac, Crohn’s
- Pregnancy, lactation, haemolytic anaemias, psoriasis
- Anticonvulsants, antifolate drugs
What are the clinical features of folate deficiency
- Insidious
- Anaemia
- Glossitis
- Mild jaundice
- No neurology
What prescription is given for folate deficiency
Oral Folic acid
What causes haemolytic anaemias
Shortened RBC survival
What RBC abnormalities can lead to haemolysis
Membrane
Haemoglobin
Enzymes
What membrane abnormalities can case haemolytic anaemias
- Hereditary Spherocytosis
- Antibodies against RBC membrane - autoantibodies, alloantibodies
What haemoglobin abnormalities can cause haemolytic anaemias
- Abnormal structure (sickle cell)
- Imbalance in synthesis? (thalassaemia)
What enzyme abnormalities can lead to haemolytic anaemias
Glucose-6-phosphate dehydrogenase deficiency
How does haemolytic anaemia present
- Pallor and anaemia
- Jaundice
- Gallstones
- Splenomegaly
What lab investigations can be found in a patient with red cell breakdown
- Increased serum unconjugated bilirubin
- Increased urobilinogen
- Increased serum lactate dehydrogenase
What lab investigations can be found in patients with hereditary spherocytosis
- Spherocytes in peripheral blood
- Decreased Hb
- Increased Lactate dehydrogenase
- Increase unconjugated serum bilirubin
What does G6PD enzyme do
Reverse the oxidation of Hb and membrane etc
What kind of inheritance does hereditary spherocytosis show
Autosomal dominant
What kind of inheritance does G6PD deficiency show
X linked
What clinical features does G6PD deficiency show
Neonatal jaundice
Acute haemolysis with oxidant drugs or fava beans
What happens when oxygen conc decreases in Sickle cell patients
- Hb forms long rod structures
- RBCs sickle
- Increased rigidity
What major problem occurs as a result of sickle celled RBCs
The cells block the microcirculation and this leads to ischaemia and pain
What causes autoimmune haemolytic anaemia
- Self reacting IgG antibody that attached to RBC and is removed by the spleen via extravascular haemolysis
How do you prove that there is an antibody on an RBC
Direct Coombs test/Direct antiglobulin test:
- Blood sample from a patient with immune mediated haemolytic anaemia and antibodies are shown to be attached to the RBC surface
- The patient’s washed RBCs are incubated with antihuman antibodies (coombs reagent)
- RBCs agglutinate: antihuman antibodies form links between RBCs by binding to human antibodies on the RBCs
What are some of the causes of immune haemolytic anaemia
- Drugs - Methyldopa, Penicillin
- Connective Tissue Disease - SLE and RA
- Cancer e.g. lymphoma
- Blood transfusion
What examinations should be done in order to investigate anaemia
- History + examinations - Drugs, family, lymph nodes, hepatosplemegaly, weight loss, sweats
- Repeat FBC and ask for blood film
- Check serum B12, folate and ferritin
- Renal and liver function
- ESR - non-specific, general inflammation/chronic disease
What are some of the potential underlying causes of microcytic anaemias
- Fe deficiency
- Thalassaemia
What are some of the potential underlying causes of normocytic anaemias
- Acute blood loss
- Chronic disease
- Cancer
- Renal disease
- Haemolysis
What are some of the potential underlying causes of microcytic anaemia
- B12/Folate deficiency
- Alcohol
- Drugs
- Liver Disease
- Bone marrow failure
- Myelodysplasia
- Haemolysis
What effects does iron deficiency have on RBCs
Leads to reduced RBC maturation as Iron required to haem synthesis and therefore reduced haemoglobin
What effects does B12/folate deficiency have on RBCs
B12 and folate required for DNA synthesis, deficiency leads to impaired maturation of the RBC nucleus causing megaloblastic, macrocytic anaemia
Describe the lab features of Haemolytic anaemia
- Increased Reticulocytes
- Increased LDH
- Increased bilirubin (unconjugated)
- Increased urinary B
- Haptoglobin
- DAT positive (in immune mediated)
