Macrocytosis and Macrocytic anaemia Flashcards
Definition of macrocytosis?
Red cells present in large numbers in a size that’s bigger than normal volume
>100fl (femtolitres)
How is RBC size measured?
MCV
Size of a normal RBC?
-appearance of normal RBC on blood film?
-80-100fl
Causes of macrocytosis
- Genuine (2)
- spurious (1)
-Megaloblastic
Non-megaloblastic
-high reticulocyte count resulting in false readings Cold agglutinins (measured as 1 giant cell)
what is a megaloblastic cell?
an abnormally large nucleated red cell precursor with an immature nucleus
describe briefly the changes an developing red cell undergoes to become a reticulocyte?
Erythroblasts are marrow based
they accumulate Hb and reduce in size
they then stop dividing and lose their nucleus
What characterises megaloblastic anaemias (3 defects, 2 preserved)?
-describe the consequences of this to the cell?
defects in DNA synthesis and nuclear maturation
preservation of RNA and Hb synthesis
-cytoplasm develops and becomes mature and big enough to divide (i.e. enough Hb) but the nucleus is still immature and lags behind
= bigger than normal red cell precursor
name the causes of megaloblastic anaemia?
B12 def
Folate def
Other:
drugs & rare inherited abnormalities
Why does B12 and folate deficiency cause megaloblastic anaemia?
they are essential co factors for nuclear maturation
they enable chemical reactions that provide enough nucleosides for DNA synthesis
i.e. nucleus cannot mature
Describe the biochemical interactions between B12 and folate
- what cycles are they involved in?
- what are the products of these cycles?
involved in the methoinian cycle and folate cycle
-methonian cycle
produces s-adenosyl methionine, a methyl donor to DNA, RNA, proteins, lipids, folate intermediates
Folate cycle
important for nucleoside synthesis (thymine)
Describe the absorption of vitamin B12?
- what happens to B12 after it has been absorbed?
- give reasons for Vit B12 deficiency? (5)
Dietary B12 is liberated from food and binds with haptocorrin B 12 then combines with intrinsic factor (secreted by gastric parietal cells) in the duodenum
the IF-B12 complex then attaches to Cubulin receptors and is absorbed in the distal bowel
passive absorption occurs through buccal, gastric and duodenal mucosae
-absorbed B12 attaches to transcobalamin (TC) II which carries B12 in plasma to the liver, bone marrow, brain and other tissues. Most B12 in plasma is, however, attached to second B12 binding protein TC I and is functional inactive
-insufficient intake- veganism stomach probs (PA, Atrophic gastritis, PPIs, Gastrectomy/bypass) Pancreatic probs (chronic pancreatitis) small bowel probs (Jejunum: bacterial overgrowth, coeliac disease Duodenum: resection, Crohn's disease) Inherited deficiency of cubulin receptors
How is folate absorbed:
- what is it converted to?
- where absorbed?
- look over table on slide 29
- causes of folate deficiency (4)
- dietary folate converted to monoglutamate
- in jejunum
-Inadequate intake (less stores than B12) Malabsorption (coeliac disease, Crohn's) Excess utilisation (Haemolysis, exfoliating dermatitis, pregnancy, malignancy) Drugs
Clinical features of B12/folate deficiency?
- Common to both? (5)
- B12 only? (1)
-signs of anaemia weight loss, diarrhoea, infertility Sore tongue- glossitis Jaundice Developmental probs
-Neurological probs Post/dorsal column abnormalities neuropathy dementia psychiatric manifestations
Pernicious anaemia
- what is it?
- associated with what?
- describe the pathogenesis
- presentation?
-autoimmune condition with resulting destruction of gastric parietal cells
these cells normally produce intrinsic factor so get B12 def
-autoimmune atrophic gastritis and personal/fam hx of autoimmune disorders
-autoimmune attack directed by dendritic cells in the stomach that normally clear apoptotic parietal cells as part of normal turnover
dendritic cells include paragastric lymph nodes, they activate CD4 cells that recognise H+/k+ ATPase expressed in gastric parietal cells
-symptoms and signs of anaemia and B12 deficiency - neuropathy etc.
Might be jaundiced due to intramedullary haemolysis (due to ineffective haemolysis)
How are megaloblastic anaemias diagnosed:
- red cells in lab?
- Blood film?
- what else should be checked?
-Macrocytic anaemia & low red cells
possible pancytopenia
-macroovalocytes and hypersegmented neutrophils (3-5 segments normally)
-Assay B12 and folate in serum
Check autoantibodies for anti gastric parietal cells and anti-intrinsic factor
