7 - Anaemia, B12 and Folate Flashcards by Leah Ashton

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

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What class of anaemia are anaemias with reticulocytosis?

Macrocytic

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What are some causes of microcytic anaemia?

Anaemia of chronic disease most commonly normocytic

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What are the different classifications of anaemia, and give some examples for each type?

Reticulocytosis not haemolytic anaemia

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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

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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

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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

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What are different cause of anaemia in general?

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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

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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)

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If you have a severe deficiency of B12 and Folate what will eventually occur secondary to anaemia?

Pancytopenia

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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

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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

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What are some issues with the reticuloendothelial system that can lead to anaemia?

- Splenomegaly: pooling of blood and RBC

- Autoimmune haemolytic anaemia with autoantibodies

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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)

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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.

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 ## Footnote **- Spleen sequestration** **- Acute blood loss**