32. Anaemia 2 Flashcards
What is macrocytic anaemia and the causes?
Oversized RBC, >96fl, cause= B12 or folate deficiency.
What are vitamin B12 and folate needed for, and what happens if they are absent?
Is vitamin B12 deficiency distinguishable from folate deficiency?
Compare B12 and folate.
DNA synthesis - to convert homocysteine to methionine. If absent -> DNA synthesis impaired -> cells don’t divide -> overlarge blood cells = macrocytic
No
B12: water soluble vitamin, in meat and eggs, not destroyed by cooking, 3yr store, absorption: bound to IF -> ilium
Folate: water soluble vitamin, in liver, greens and yeast, destroyed by cooking, 4m store, absorption: duodenum and jejunum. Rarer than B12 deficiency
Both: macrocytic anaemia if deficient
How is vitamin B12 absorbed?
Usually bound to protein in foods, released by stomach acid, binds to IF (intrinsic factor). The IF-B12 complex is absorbed by receptors on ileum epithelial cells.
What produces intrinsic factor?
B12 and folate deficiencies look identical. What would be observed in:
a) blood count?
b) blood film?
c) biochemistry?
Intrinsic factor is produced by parietal cells of gastric mucosa
a) decreased Hb, WBC and platelets, increased MCV (>120)
b) oval macrocytes and hypersegmented neutrophils (>4 lobes)
c) increase in lactate dehydrogenase and bilirubin (due to haemolysis)
Describe the cell and possible diagnosis.
Hypersegmented neutraphils. Macrocytic anaemia - B12/folate deficiency
What are the 2 main causes of B12 deficiency?
Describe pernicious anaemia.
1) nutritional 2) malabsorption (gastric = pernicious anaemia/ surgical gastrectomy, or intestinal = ileal disease e.g. Chrons - IBD)
Autoimmune disorder, 1-2% >60y, F>M, associated with blood type A, due to autoantibody against gastric mucosa and IF, leads to gastric atrophy, decreased acid and IF secretion - not absorbing Fe
What are the clinical features of pernicious anaemia?
What is the treatment?
What would lab investigations show?
Insidious, anaemia, glossitis (tongue inflammation), mild jaundice (haemolysis - high bilirubin levels), neurological symptoms (B12 only: peripheral neuropathy, damage to sensory and motor tracts, dementia, optic atrophy)
Treatment: intramuscular B12 every 3m for life
Macrocytic anaemia, hypersegmented neutrophils, decreased serum B12
What are the 4 causes of folate deficiency?
(Found in meat, vegetables, grains and nuts)
1) nutritional (age, poverty, alcoholism)
2) malapbsorption (coeliac, chron’s)
3) excess utilization (pregnancy, lactation, haemolytic anaemia, psoriasis)
4. other (antconvulsants)
What are the clinical features of folate deficiency?
What is the treatment?
What is haemolytic anaemia?
What are the effects of haemolytic anaemia?
Insidious, anaemia, glossitis, mild jaundice, no neurological signs
Oral folic acid
Caused by shortened RBC survival - lifespan = <120 days
Increased lactate dehydrogenase (enzyme inside RBC), radiolabelled RBC to measure lifespan, increased reticulocytes, gallstones (if longterm), increased bilirubin
Describe the 3 abnormalities of RBC that can cause haemolysis?
1) Damage to membrane: hereditary spherocytosis (cells stay spherical - don’t go through capillaries easily and break up), oxidising agents, antibodies against membrane: autoantibodies/alloantibodies (transfusion rxn)
2) Damage to Hb: abnormal structure (sickle cell), imbalance in alpha:beta synth (thalassaemia)
3) Changes to enzymes in cell: glucose 6 phosphate dehydrogenase (one of RBC’s enzymes for glycolysis - if deficient, RBC have shorter life)
Snakebites and infections can also cause intravascula haemolysis
What is the presentation of haemolytic anaemia?
What would be seen in the lab?
Pallor and anaemia, jaundice, gallstones, splenomegaly
RBC breakdown: increased serum unconjugated bilirubin, urinary urobilinogen and lactate dehydrogenase.
Increased RBC production: increased reticulocytes in blood and RBC in marrow (pic)
What is hereditary spherocytosis?
What are the clinical features?
Autosomal dominat. A RBC membrane defect in proteins of RBC cytoskeleton = contracts to its most surface-tension efficient and least flexible configuration = a sphere. Spherocytes have smaller SA but maintain healthy O2 supplies, BUT have high fragility and are more prone to degradation e.g. when passing through capillaries.
Chronic haemolytic anaemia, spherocytes visible in peripheral blood film, deacreased Hb, increased LDH and unconjugated serum bilirubin
What is G6PD deficiency?
How do G6PD carriers fare?
RBC enzyme defect. X-linked. Hb and other RBC proteins become oxidised over time due to high pO2, G6PD prevents/reverses oxidation of Hb, membrane etc. prolongs life of RBC.
(Glucose-6-phosphate dehydrogenase)
No symptoms unless RBC exposed to certain triggers, then haemolysis:
1) food (fava beans etc.)
2) bacterial/viral infection
3) drugs e.g. antimalarials - dapsone etc.
What can you see in this blood film, and what is a possible diagnosis?
RBCs oxidised and damaged, haemolytic anaemia
What is autoimmune haemolytic anaemia?
How would you prove there is an antibody on a RBC?
What are the causes of
a) idiopathic AIHA?
b) secondary AIHA?
IgG antibodies present in blood that react with RBC membrane proteins - affected RBCs then removed by spleen (extravascular haemolysis)
Dirct Coombs/antiglobulin test - washed RBCs incubated with antihuman antibodies -> RBCs agglutinate if positve.
a) unknown - 50%
b) drugs e.g. antimalarials, penicillin, CT disease e.g. systemic lupus erythematosus, blood transfusion
