Macrocytic anaemia and vitamin B12 and folate Flashcards
1
Q
Macrocytic anaemia
A
- Anaemias where the average red cell size is greater than normal (increased MCV)*
- >100 fl*
2
Q
types of maxcrocytic anaemia
A
- Megaloblastic anaemia
- Macronormoblastic erythropoiesis
- Stress erythropoiesis
3
Q
causes of macrocytic anaemia
A
- vitamin B12 anaemia
- Folate deficiency
- myelodysplasia
- liver disease
- alcohol toxicity
4
Q
Megaloblastic anaemia
A
- Interference with DNA synthesis during erythropoiesis causes development of nucleus to be retarded in relation to maturation of cytoplasm
- Cell division delayed and erythroblasts continue to grow to form megaloblasts which give rise to larger red cells
5
Q
causes of megaloblastic anaemia
A
- Vitamin B12 / folate deficiency
- Drugs that interfere with DNA synthesis (e.g. some anti- cancer)
- Some erythroid leukaemias where DNA synthesis is retarded
6
Q
A
7
Q
Macronormoblastic erythropoiesis
A
Normal relationship between development of nucleus and cytoplasm is retained but erythroblasts are larger than normal and give rise to larger red cells
8
Q
cause of macronormoblastic erythropoiesis
A
- liver disease
- alcohol toxicity
- myelodysplastic syndrome
9
Q
Stress erythropoiesis
A
- Conditions associated with a high reticulocyte count (reticulocytes are larger than normal red cells)
- High level of erythropoietin leads to an expanded and accelerated erythropoiesis
10
Q
causes of stress erythropoiesis
A
- Recovery from blood loss due to haemorrhage
- Recovery from haemolytic anaemia
11
Q
folate is the
A
synthetic form of folic acid
12
Q
what synthesises folate
A
bacteria and plants
13
Q
what are good sources of folate
A
- Present in a wide variety of animal and vegetable food sources
- Green leafy vegetables (foliage)
14
Q
where is folate absorbed
A
duodenum and jejunum
15
Q
once the folate has been absorbed in the duodenum and jejunum what is it converted to
A
- tetrahydrofolate (FH4) by intestinal cells
- Taken up by liver- store
16
Q
importance of folate
A
- Metabolic role to provide carbons for other reactions
- E.g. synthesis of nucleotides bases required for DNA and RNA synthesis
17
Q
cause of folate deficiency
A
- Dietary deficiency (poor diet)
-
Increased requirements
- Pregnancy
- Increased erythropoiesis e.g. haemolytic anaemia
- Severe skin disease e.g. psoriasis
- Disease of duodenum and jejunum (e.g. coeliac disease and crohns disease)
- Drugs which inhibit dihydrofolate reductase e.g. methotrexate
- Alcoholism
- Urinary loss of folate in liver disease and heart failure
18
Q
symtoms of folate deficiency
A
- Anaemia related
- Reduced sense of taste
- Diarrhoea
- Numbness and tingling in feet and hands
- Muscle weakness
- Depression
19
Q
why is folic acid taken before conception and during the first 12 weeks of pregnancy
A
to prevent neural tube defects in babies e.g. spina bifida
20
Q
vitamin B12 is also known as
A
cyancobalamin
21
Q
what sort of vitamin is Vitamin B12 (cyanocobalamin)
A
Water soluble vit
22
Q
vitamin B12 is an
A
- essential cofactor fo DNA synthesis (due to its role in folate metabolism)
- required for normal eryhtropoiesis
- essential for normal function and development of the CNS
23
Q
what produces vitamin B12
A
bacteria
24
Q
sources of B12
A
- Largely obtained from foods of animal origin (produced by commensal bacteria)
- Essential that people on a vegan diet eat foods fortified with B12 or take a B12 supplement daily or weekly
25
vitamin B12 absorption
1. **B12 r**eleased from food proteins by **proteolysis** in stomach where it then binds to **haptocorrin**
2. **Haptocorrin B12 complex** digested by pancreatic proteases in small intestine releasing B12 which then **binds intrinsic factor** (produced by gastric parietal cells).
3. **Intrinsic factor–B12 complex binds to cubam receptor** which mediates uptake of complex by receptor- mediated endocytosis into enterocytes
4. After lysosomal release in enterocytes, B12 exits via basolateral membrane through **MDR1**
5. Binds to **transcobalamin** in blood and transported around bloodstream
6. Majority of **B12 is stored in the liver (**store enough to provide B12 requirements for ~3-6 years)
26
pernicious anaemia
* Decreased or absent intrinsic factor (causes progressive exhaustion of B12 reserves
27
cause of pernicious anaemia
* Autoimmune disease
* 2 types of antibody
* Blocking Ab blocks binding of B12 to IF
* Binding Ab prevents receptor mediated endocytosis
28
causes of vitamin B12 deficeincy
* Dietary deficiency
* Lack of intrinsic factor (Pernicious anaemia)
* Disease of the ileum (Crohns disease, ileal resection, tropical sprue)
* Lack of transcobalamin (congenital defect)
* Chemical inactivation of B12 e.g. frequent use of anaesthetic gas nitrous oxide
* Parasitic infestation (tapeworm can trap b12)
* Some drugs can chelate intrinsic factor (e.g. hypercholesterolaemia drug cholestyramine)
29
symptoms of B12 deficiency
* Anaemia related
* Glossitis and mouth ulcers
* Diarrhoea
* Paraesthesia
* Disturbed vision
* irritability
30
how can B12/folate deficiency also affect the NS
* Folate deficiency in pregnancy can cause neural tube defects
* Vitamin B12 deficiency associated with focal demyelination
**Subacute combined degeneration of the cord**
31
B12 defiicency more often resuls in
reversible peripheral neuropathy
32
which serious condition can B12 deficiency result in
* subacute combined degeneration (irreversible) of the cord- involving degeneration of posterior and lateral columns of the spinal cord
33
symptoms of subacute combined degeneration of the cord
* Gradual onset weakness, numbness and tingling in arms, legs and trunk which progressively worsens
* Changes in mental state
34
relationship between B12 and Folate
lack of B12 will trap folate in the stable methyltetrahydrofolate form prveneting its use in other reactions such as synthesis of thymidine for DNA synthesis
35
Why do B12 and folate deficiency cause a megaloblastic anaemia?
* Both folate and B12 deficiency lead to thymidine deficiency
* In absence of thymidine, uracil is incorporated into DNA instead
* DNA repair enzymes detect these errors and constantly repair excision
* Results in **asynchronous maturation** between nucleus and cytoplasm
* Nucleus doesn’t fully mature
* Cytoplasm matures at the normal rate
* Large nuclei and open chromatin
* Mature red cells also large leading to macrocytic anaemia
36
megaloblastic features in peripheral blood film
As B12/foalte deficiency progresses a **pancytopenia** ca also develop i.e. low platelets and neutrophils as well
37
Investigations for megaloblastic anaemia
38
treatment of vitamien B12 and folate deficiency
