Microcytic and haemolytic anaemia Flashcards
why is vitamin B12 called cobalamin
- it contains cobalt metal
Is vitamin B12 water soluble or not
- water soluble
what can prolonged deficiency of vitamin B12 cause
- Prolonged vitamin B12 deficiency can cause severe and irreversible nervous system damage
what can only slightly lower than normal levels of B12 cause
- a range of symptoms such as fatigue, lethargy, depression, poor memory, breathlessness, headaches, and pale skin may be experienced, especially in elderly people
what is the function of B12
- production of myelin
- assits in DNA synthesis
- Methionine synthase is an enzyme which uses B12 to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine, thereby generating tetrahydrofolate (THF) and methionine
- THF plays an important role in DNA synthesis so reduces the availability of te THF results in ineffective production of cells with rapid turnover in particular RBC
- THF can be obtained from folate in the diet – this can compensate from the blood problems but not he brain problems
what anaemia does B12 cause
- macrocytic
what are the two types of anaemia
megaloblastic and non-megaloblastic anaemia
how can B12 deficiency be measured
- B12 deficiency can be measured clinically as an increased serum methylmalonic acid (MMA) level.
- Unfortunately, this is not a foolproof test as not all who have increased MMA actually have B12 deficiency.
what part of B12 deficiency can be cured by folate
- The reduced DNA synthetic effects of B12 deficiency can be resolved if sufficient dietary folate is present
- However the reduced myelin synthesis seen with B12 deficiency is NOT cured by folate.
define megaloblastic anaemia
is macrocytic anaemia that results from inhibition of DNA synthesis during red blood cell production
describe vitamin B12
- water soluble?
- what food is it found in
- is it destroyed by cooking
- is deficiency indistinguishable from folate deficiency
- require
- store
- absorption
- Water soluble vitamin
- Found in Meat, eggs, cheese animal protein
- Not destroyed by cooking
- Deficiency initially indistinguishable from folate deficiency
- Requires – 1 ug/d
- Store – 1000ug (3 years)- body stores B12 efficently therefore a temporary loss doesn’t effect as you can have a long store
- Absopriton – binds to intrinsic factor in the ileum
describe vitamin B9 (folate)
- water soluble?
- what food is it found in
- is it destroyed by cooking
- is deficiency indistinguishable from B12 deficiency
- require
- store
- absorption
- Water soluble vitamin
- Liver, greens, yeast
- Destroyed by cooking* - prolonged boiling or deep frying
- Deficiency mostly indistinguishable from B12 deficiency
- Require – 150ug/d
- Store – 4 months
- Absorption – duodenum and jejunum
why does vitamin B12 or folate deficiency lead to cell failure
- This leads to DNA synthesis impaired
- Cells then fail to divide in the proerythroblast stage and therefore they get to big
- Cannot get through capillary in the muscles and other tissues
- Increased rate of destruction of red cells as they are too big therefore they lysis
- Then you get Anaemia signs and symptoms
how is B12 absorbed
- Vitamin B12 is usually bound to protein in foods and is released by stomach acid.
- Following its release, B12 is absorbed in the ileum when binding to intrinsic factor (IF).
- The intrinsic factor-B12 complex is absorbed by receptors on the ileum epithelial cells.
what produces intrinsic factor
Intrinsic factor is produced by parietal cells* of the gastric mucosa
What is anaemia caused by B12 malabsorption characterised
- Pernicious anaemia characterized by B12 deficiency is often caused by the absence or reduction of intrinsic factor(may be due to autoimmune disease).
how is the ileum separated from the cecum
- It follows the jejunum and is separated from the cecum by the ileococal valve (ICV) at the ileo-cecal junction
how long is the ileum
2-4m
what do B12 an folate deficiencies share in blood tests
- low haemoglobin
- high MCV
- low WBC and platelets
- macrocytes
- hypersegemetned neutrophils
- increased lactate dehydrogenase
- increased bilirubin
what does it mean if lactate dehydrogenase and bilirubin increases
- test for haemolytic anaemia
what is a hypersegemented neutrophil
- this is a neutrophil with an increased number of lobes, it has more than 6 lobes
what are the main causes of a B12 deficiency
- Nutritional – poor vegan diet
Malabsorption
– either gastric due to pernicious anaemia and surgical gastrectomy
- intestinal – ileal disease such as crohnS
What is crohns disease
- chronic inflammatory disorder which the bodies immune system attacks the GI tract
- possibly directed at microbial antigens
describe the features of pernicious anaemia
- An autoimmune disorder
- Incidence is 1-2% in population > 60 years
- F > M
- Associated with fair hair, blue eyes, blood group A
- Due to an Autoantibody against parietal cells and intrinsic factor (IF)
- Leads to gastric atrophy, ↓ acid + ↓ IF secretion
what are the clinical features of pernicious anaemia
• Insidious (gradual onset but fatal if untreated) • Anaemia • Glossitis (inflammation of tongue) • Mild jaundice • Neurological Symptoms – Peripheral neuropathy – Damage to Sensory and Motor tracts – Dementia – Optic atrophy – Pins and needles parathethesia – treatment: intramuscular B12 every 3 months for life
what do the lab tests show for pernicious anaemia
- microcytic anaemia
- hypersegemented neutrophils
- decreased serum B12
what are the causes of folate deficiency
- nutritional – old age, poverty, alcoholism
- malabsorption – coeliac, crohns
- excess utilization – pregnancy, lactation, haemolytic anaemia, psoriasis
- others – anticonvulsants
- Folate deficiency clinical features are same as for pernicious anaemia but without neurological symptoms.
what is the treatment for folate deficiency
- oral folic acid
what is haemolytic anaemia
- this is when the RBC has a lifespan of less than 120 days
what does increased bilirubin cause
jaundice
what can long standing haemolysis cause
gall stones
what is haemosiderin
it is a ferritin that is denatured and therefore cannot release the iron
what are the tests for haemloysis
tests in the urine for
1, urobilinogen
2, haemosidirin
what is the presentation of haemolytic anaemia
- Pallor and signs/symptoms of anaemia
- Jaundice
- Gallstones
- Splenomegaly
- Levels of bilirubin in blood are normally below 17umol/L but here levels are over 34-51 umol/L which typically result in jaundice
what are three causes of haemolytic anaemia
- Membrane
- Haemoglobin
- Enzymes
describe membrane as an haemolytic cause of anaemia
- Hereditary spherocytosis – stay as a sphere, and don’t shrink to there adult form
- Oxidising agetns
- Antibodies against RBC membrane
- Autoantibodies
- Alloantibodies – transfusion rxn – happens if you give someone the wrong blood
describe haemoglobin as an haemolytic cause of anaemia
- Abnormal structure such as sickle cell disease
- Imbalance in Alpha and Beta synthesis such as in thalassaemia
describe enzymes as a haemolytic cause of anaemia
- Glucose-6-phosphate dehydrogenase
- Haemoglobin & other RBC proteins become oxidised over time due to high PO2 – eventually they are converted to methaemoglobin
- G6PD prevents/reverses oxidation of Hb, membrane etc; prolongs lifetime of RBC.
what is hereditary spherocytosis caused by
- This is caused by a defect in the proteins of the red blood cell cytoskeleton. Because of this defect, the blood cell contracts to its most surface-tension efficient and least flexible configuration, a sphere
- they have smaller surface area and can perform adequately to maintain a healthy oxygen supply but they have high fragility and therefore are prone to physical degradation when they pass through capillaries
what are the clinical features of hereditary spherocytosis
- Autosomal dominant
- Chronic haemolytic anaemia
- Spherocytes visible in peripheral blood film
- ↓ Hb, ↑ LDH, ↑ unconjugated serum bilirubin
describe Glucose 6-phosphate dehydrogenase genetic features
- 400 million people worldwide have deficiency
- Tropical Africa, Middle East, subtropical Asia, Mediterranean
- X-linked
- 400 different mutations
what would show in a lab result if there is increased red cell breakdown
- Increased serum unconjugated bilirubin
- Increased urinary urobilinogen
- Increased lactate dehydrogenase
what would show in a lab result if there was increased red blood cell production
- Reticulocytes in the blood
- Increased RBC in marrow
What things trigger a G6PD symptoms to show
- Carriers of the underlying mutation do not show any symptoms unless their RBC are exposed to certain triggers which are
- 1) foods (fava beans is one of them),
- 2) Bacterial or viral infection
- 3) Drugs eg dapsone, cotrimoxazole and primaquine
how can an autoimmune condition cause haemolytic anaemia
- IgG antibodies are present in blood that react with RBC membrane proteins
- IgG antibody attaches to RBC and labels for destruction
- Labelled RBCs then removed by spleen (Extravascular haemolysis)
how do you check if there is an antibody on red cell
- take a blood sample from a patient with immune mediated haemolytic anaemia
- patients washed RBC are incubated with antihuman antibodies (Coombs reagent)
- RBC agglutinate, antihuman antibodies form links beween RBCs by binding to the human antibodies on the RBCs
