Macrocytic And Haemolytic Anaemias Flashcards
What mechanisms can cause anaemia
Decr/dysfunctional erythropoiesis
Abnormal Haem synthesis
Abnormal globin chain synthesis
Abnormal RBC structure
RBC mechanical damage
Abnormal RBC metabolism
Excessive bleeding
Increased removal
How can vitamin deficiencies cause anaemia
Reduce erythropoiesis
Anaemia
Hb level below reference level for age and sex
What are the 3 classes of anaemia based on RBC size
Macrocytic
Normocytic
Microcytic
3 types of macrocytic anaemia
Megaloblastic anaemia
Macronormoblastic erythropoiesis
Stress erythropoiesis
When does stress erythropoiesis occur
After haemorrhage
Characteristics of megaloblasts
Bigger than normal RBCs
Large immature nuclei
What causes megaloblastic anaemia
Interference with DNA synthesis during erythropoiesis
Why do erythrocytes continue growing to form megaloblasts in megaloblastic anaemia
Cell division delayed due to delayed nucleus development
What can lead to megaloblastic anaemia
Vitamin B12 deficiency
Folate deficiency
Drugs
Some erythroid leukaemias
How are erythroblast abnormal in macronormoblastic erythropoiesis
Larger than normal
What conditions can lead to macronormoblastic anaemia
Liver disease
Alcohol toxicity
Some myelodysplastic syndromes
What is Stress erythropoiesis and what type of cell has a higher than normal count when it occurs
Increased erythropoiesis in response to blood loss
Reticulocyte
What causes expanded and accelerated erythropoiesis in stress erythropoiesis
High erythropoietin levels
What can lead to stress erythropoiesis
Recovery from Blood loss/haemorrhage
Recovery from haemolytic anaemia
What foods are high in folate
Green leafy veg
Citrus
Avocados
Other veg
Fortified cereals
Where is folate mainly absorbed
Duodenum
Jejenum
Which cells convert folate to tetrahydrofolate
Intestinal cells
Where is folate taken up and stored
Liver
What is folate needed for
Provide carbon for metabolic reactions - nucleotide base synthesis, DNA synthesis, RNA synthesis
Folate deficiency causes
Dietary deficiency
Increased requirements
Disease of duodenum or jejenum
Drugs which inhibit dihydrofolate reductase
Alcoholism
Liver disease
Heart failure
Folate deficiency symptoms
Anaemia related symptoms
Reduced sense of taste
Diarrhoea
Numbness and tingling in hands and feet
Muscle weakness
Depression
When and how much folic acid should be taken in regards to pregnancy
400ug/day
Before conception - 12wks
Why should folic acid be taken in early pregnancy
Prevents neural tube defects
What role does vitamin b12 play in DNA synthesis
Cofactor
What is vitamin B12 needed for
DNA synthesis
Erythropoiesis
CNS myelination
BCAA metabolism
FA metabolism
Which foods are sources of vitamin b12
Foods of animal origin
Which people require daily vitamin b12 supplements
Vegans
What does vitamin b12 bind to in the stomach
Haptocorrin
Where is intrinsic factor produced
Gastric parietal cells in stomach
Where does intrinsic factor bind to vitamin b12
Small intestine
Where is vitamin b12 taken up by the body
Terminal ileum
How is vitamin b12 taken up into cells
Receptor mediated endocytosis via Cubam receptor
What does vitamin b12 bind to in the blood for transport
Transcobalamin
Where is the majority of vitamin b12 stored
Liver
Vitamin b12 deficiency causes
Dietary deficiency
Lack of intrinsic factor
Disease of ileum
Lack of transcobalamin
Chemical inactivation of b12
Parasitic infestation
Intrinsic factor chelating drugs
Pernicious anaemia
Autoimmune disease that creates antibodies to intrinsic factor or parietal cells
What drug can chemically inactivate vitamin b12
Nitrous oxide
B12 deficiency symptoms
Anaemia related symptoms
Glossitis
Mouth ulcers
Diarrhoea
Paraesthesia
Disturbed vision
Irritability
Mental status change
Paraesthesia
Burning/prickling sensation usually felt in hands feet arms or legs
Is pernicious anaemia more common in men or women
Women
What does pernicious anaemia lead to
Gastric atrophy
Decreased acid
Decreased intrinsic factor secretion
How can folate deficiency affect the nervous system
Neural tube defects in pregnancy
How can vitamin b12 deficiency affect the nervous system
Focal demyelination
Reversible peripheral neuropathy
Subacute combined degeneration of the cord
Subacute combined degeneration of the cord
Degeneration of posterior and lateral columns of the spinal cord caused by b12 deficiency
Subacute degeneration of the cord symptoms
Gradual onset weakness
Numbness and tingling in arms legs and trunks
Mental state changes
How do vitamin b12 or folate deficiencies cause megaloblastic anaemia
Defective DNA synthesis -> nucleus matures slower than cytoplasm -> nucleus keeps getting bigger -> megaloblastic cells
How can elevated folate intake mask vitamin b12 deficiency
Alleviates anaemia caused by b12 deficiency by providing continual supply of active folate, as b12 needed to regenerate active folate
Why is folate masking of vitamin b12 deficiency dangerous
B12 deficiency may still cause Irreversible neurological damage
What is seen in a peripheral blood smear of a patient with megaloblastic anaemia
Large RBCs w large immature nuclei
Hyper segmented neutrophils
How is megaloblastic anaemia diagnosed
Blood smear
Check vitamin b12 and folate
Full blood count
Check for anti intrinsic factor antibodies
How is folate deficiency treated
Oral folic acid
How is vitamin b12 deficiency due to pernicious anaemia treated
Intramuscular hydroxycobalamine for life
How is vitamin b12 deficiency not related to pernicious anaemia treated
Oral cyanocobalamine
How long does it take for neuropathy caused by vitamin b12 deficiency to resolve after treatment begins
3-6 months
May not resolve if deficient for too long
What can blood transfusions cause in patients with sever anaemia from b12 deficiency
High output cardiac failure
What causes haemolytic anaemia
Abnormal haemolysis
Intravascular haemolysis
RBC breakdown in blood vessels
Extravascular haemolysis
RBC breakdown in spleen and wider RES
How can bone marrow compensate for abnormal haemolysis to prevent haemolytic anaemia
Increase RBC production up to a point
Inherited causes of haemolytic anaemia
Glycolysis defect
Pentose P pathway defect
Membrane protein defect
Haemoglobin defect
Acquired haemolytic anaemia causes
Mechanical damage to cells
Antibody damage to cells
Oxidant damage to cells
Heat damage to cells
Enzymatic damage to cells
What laboratory findings are linked to haemolytic anaemia
Raised reticulocytes
Raised bilirubin
Raised LDH
Pathology at which 3 sites can can haemolytic anaemia
RBC membrane
haemoglobin
RBC enzymes
Haemolytic anaemia signs and symptoms
Jaundice
Pigment gallstones
Splenomegaly
What causes jaundice
Accumulation of bilirubin
What causes splenomegaly in haemolytic anaemia
Extramedullary hematopoiesis in red pulp spleen
Extramedullary hematopoiesis
Making blood outside bone marrow
What can be caused by massive sudden haemolysis
Cardiac arrest
Hyperkalaemia
What are 3 inherited defects in RBC membranes that can cause haemolytic anaemia
Hereditary spherocytosis
Hereditary eliptocytosis
Hereditary pyropoikilocytosis
What shape are RBCs in hereditary spherocytosis
Spherical
What shape are RBCs in herditary eliptocytosis
Elliptical
What shape are RBCs in herditary pyropoikilocytosis
Elliptical
What defects cause hereditary spherocytosis
Ankyrin, spectrin, protein 4.2, band 3
What protein is defective in hereditary eliptocytosis and hereditary pyropoikilocytosis
Spectrin
What is the more severe form of hereditary eliptocytosis
Hereditary pyropoikilocytosis
What are RBCs abnormally sensitive to in hereditary pyropoikilocytosis
Heat
What enzyme deficiencies can cause haemolytic anaemia
Pyruvate kinase
Glucose 6 phosphate dehydrogenase
How can pyruvate kinase deficiency cause haemolytic anaemia
Stops final step of glycolysis decreasing ATP production, which prevents ATPase pump functioning causing loss of K+ and H2O, causing dehydrating and cell death
Why does pyruvate kinase deficiency usually only cause mild haemolytic anaemia
Still some enzyme activity present
Increased 2,3 DPG levels
How does glucose 6 phosphate dehydrogenase deficiency cause haemolytic anaemia
Limits pentose phosphate pathway -> decreased NADPH levels ->glutathione not kept in reduced state -> RBCs very affected by oxidative stress -> haemolysis
Heinz bodies
Clumps of oxidised haemoglobin
How can Heinz bodies damage RBCs
May detach and damage membrane
Which conditions cause Heinz body formation
Glucose 6 phosphate dehydrogenase deficiency
Thalassaemias
What causes microangiopathic anaemias
Mechanical damage to RBCs
How can RBCs be mechanically damaged
Shear stress from passing through defective heart valves
Snagging on fibrin strands in small vessels with increased activation of clotting cascade
What acquired damage to RBCs can cause haemolytic anaemia
Mechanical damage
Heat damage
Osmotic damage
Schistocytes
RBC fragments from mechanical damage
How can autoimmune RBC destruction cause haemolytic anaemia
Autoantibodies bind to RBCs -> spleen removes antibody bound cells
What is autoimmune haemolytic anaemia classified as warm or cold based on
Temperature antibodies react most strongly under laboratory conditions
What conditions can cause autoimmune haemolytic anaemia
Drugs
Connective tissue disease
Lond transfusion
Cancer of lymphoid system
Infections
Can b12 deficiency cause neurological symptoms without causing anaemia
Yes
