7 - Anaemia, B12 and Folate Flashcards
How is vitamin B12 absorbed?
- Obtained from animal origin so vegans need supplement
- B12 binds to haptocorrin from salivary glands
- Parietal cells in stomach release intrinsic factor and HCl
- Haptocorrin B12 complex digested by pancreatic proteases in SI
- Release B12 binds to glycoprotein IF
- In terminal ileum B12-IF complex binds to receptors
- Once internalised B12 binds to transcobalamin II to be delivered in blood to tissues with receptor for complex
What class of anaemia are anaemias with reticulocytosis?
Macrocytic
What are some causes of microcytic anaemia?
- Anaemia of chronic disease most commonly normocytic
What are the different classifications of anaemia, and give some examples for each type?
Reticulocytosis not haemolytic anaemia
What is the definition of anaemia and what are some symptoms?
- Hb concentration lower than normal range, depending on age, sex and ethnicity
- Acute symptoms: fatigue, dysponea, palpitations and headache. Underlying vascular disease may have angina and intermittent claudication
- Long term signs: pallor, tachycardia, tachypnoea, hypotension
What are some defects in haemoglobin synthesis that lead to anaemia?
- Deficiences in essential nutrients, e.g iron, B12, folate
- Globin gene mutations, e.g thalassaemia
- Anaemia of chronic disease e.g causing iron deficiency
What do you need to be careful of when given vitamin B12 deficient patients transfusions and IM injections?
- Hypokalaemia due to increased RBC production
- Cardiac failure with transfusion as heart will be more muscular to combat Vit B12 anaemia
What are different cause of anaemia in general?
Why are symptoms of anaemia not that bad if they develop over a long period of time?
Body has time to adjust by increasing cardiac stroke volume and increase concentration fo 2,3-BPG
What is sideroblastic anaemia?
Inherited disorder where ringed sideroblasts are produced by bone marrow as bone marrow cannot incorpate iron into haemoglobin as it is trapped in the mitochondria
(Iron around normoblast nucleus)
If you have a severe deficiency of B12 and Folate what will eventually occur secondary to anaemia?
Pancytopenia
What is megaloblastic anaemia?
Associated with B12 and Folate deficiency as they are building blocks in DNA synthesis so nuclear maturation and divison lag behind cytoplasm growth
- Macrocytic RBC
- Anisopoikilocytosis with tear drops and ovals
- Hypersegmented neutrophils
PICTURE BELOW WITH LARGE NUCLEI WITH OPEN CHROMATIN IN BONE MARROW
Why can abnormal metabolism in red blood cells cause anaemia?
- No ATP produced to maintain the cell integrity so membrane is damaged and spleen removes
- Glucose-6-phosphate dehydrogenase deficiency
- Pyruvate Kinase deficiency
What are some issues with the reticuloendothelial system that can lead to anaemia?
- Splenomegaly: pooling of blood and RBC
- Autoimmune haemolytic anaemia with autoantibodies
What are some causes of macrocytic anaemia with low reticulocyte count?
- Liver disease
- Myelodysplasia
- Liver disease
- B12 and Folate deficiency
- Hypothyroidism
- Alcohol
(non megaloblastic means no issue with DNA synthesis)
What would a blood count show if a patient has a haemolytic disorder?
- High MCV
- High reticulocyte count
- High LDH (marker of cell turnover)
- High bilirubin
What are some common haemolytic anaemias and what are they caused by?
- Hereditary: Spherocytosis, Eliptocytosis, Pyropoikilocytosis
- Mechanical Damage: Heart valves, DIC, MAHA
- Heat damage: burn victims
- Osmotic change: drowning
What is vitamin B12 needed for in the body?
- Transfer methyl group from L-methylmalonyl CoA to form Succiny CoA
- Transfer methyl group from FH4 to homocysteine to form methionine
Functional folate deficiency as without B12 folate would be trapped in stable form, FH4
When a patient has a low Hb count, how should you evaluate the cause of anaemia?
What are two conditions that have multifactorial causes of anaemia?
Myelofibrosis: Fibrosis in bone marrow so cannot produce RBC as no space so haemopoiesis moves to spleen. Splenomegaly causing pooling of RBC. Tear drop cells
Thalassemia: Not producing enough RBC’s and they have a weird shape. RES removes weird RBC with low Hb. Leads to splenomegaly and therefore pooling
What is pernicious anaemia?
Autoimmune disease against parietal cells so IF not produced so Vit B12 cannot be absorbed
What are some common chronic diseases causing anaemia?
- Renal disease
- Inflammatory arthiritis
- IBS
When does intravascular destruction of red blood cells occur?
During blood transfusion of red blood cells with different blood type. Autolyse
What symptoms can folate and vitamin B12 deficiency cause?
- Folate: Neural tube defects, neurological disease
- Vitamin B12: Subacute combined degeneration of the cord in posterior and lateral columns. Weakness and tingling to eventual irreversible change in nervous syystem and change in mental state.
or
Reversible peripheral neuropathy
What are some specific physical signs of anaemia?
- Plummer Vinson syndrome
- Angular stomatitis
- Koilonychia
- Glossitis
DON’T OFTEN SEE AS CAUGHT EARLY
How do you treat Vitamin B12 and Folate deficiencies?
Vitamin B12
- Hydroxocobalamin by IM injection on alternate days for 2 weeks then once every 3 months. If deficiency of IF
- Diet related can be oral cyanocobalamine
Folate
- Oral daily for 4 months to correct
- Check B12 levels before treatment as could mask a neurological disease
Why is there delayed DNA maturation with megaloblastic anaemia?
- Lack of vit B12 and folate leads to thymidylate deficiency so uracil gets incorporated into DNA instead of thymine leading to destruction of DNA by enzymes
- Asynchronus maturation between nucleus and cytoplasm
How are vitamin B12 and folate linked?
- Vit B12 converts folate to THF that the body can use
- THF needed for serin-glycine conversion, histidine catabolism, purine synthesis, thymidylate synthesis
- Vit B12 needs folic acid to reduce homocysteine to methionine which is used to make SAM (production of neurotransmitters and DNA methylation)
What are some clues of anaemia of inflammation or chronic disease?
- Increased CRP
- Increased ferritin
- Low Hb
What are some causes of dyserythropoiesis that can lead to anaemia?
- Chronic kidney disease: insufficient erythropoietin levels
- Bone marrow has cancer cells
- Myelofibrosis
- Empty bone marrow: e.g parvovirus, aplastic anaemia, radiation, autoimmunity, chemo, benzene
- Myelodysplastic syndrome (MDS)
- Anaemia of Inflammation/Chronic Disease: iron not released for bone marrow, in macrophages. Reduced life span of RBC. Marrow has lack of response to EPO
Where do you get folate from in the diet and what can deficiency be caused by?
- Yeast, liver, leafy greens
- 5mg stores for 3-4 months supply
- Absorption in duodenum ansd jejunum
What is folate needed for in the body?
- Once absorbed it is converted to tetrahydrofolate and is then stored in liver or act as one carbon carrier
- FH4 accepts carbon from sources like serine and glycine and transfers the carbons from the ‘one-carbon pool’
- Synthesis of thymidine, adenine and guanine and transfers methyl groups to B12
What are some causes of low vitamin B12?
- Dietary deficiency
- Lack of IF (pernicious anaemia, gastrectomy)
- Disease of the ileum (Chrohn’s)
- Lack of transcobalamin II (congenital)
What are some causes of normocytic anaemia with low reticulocyte count?
- Primary bone marrow failure (rare e.g aplastic anaemia)
- Secondary bone marrow failure (e.g
What are some causes of anaemia that present with reticulocytosis?
- Haemolysis: autoimmune, enzyme defects, membrane defects, mechanical
- Spleen sequestration
- Acute blood loss
