B12, Folate + Iron Flashcards
Where is folate synthesised in?
Bacteria + plants
Where is folate mainly absorbed from?
Duodenum
Jejunum
Outline the path of folate in the body
- eaten
- absorbed mainly from duodenum + jejunum
- converted to tetrahydrofolate by intestinal cells
- taken up by liver which acts as a store
Where is folate stored?
How long does it last?
How fast is it used up in anaemia?
Liver
3-4 months
Anaemia - 2 to 3 weeks
Causes of folate deficiency
- Poor diet
- Increased requirement - pregnancy, increased erythropoiesis
- Disease of duodenum or jejunum e.g. Crohn’s disease, coeliac disease
- Alcoholism
- Liver disease or heart failure - urinary loss of folate
Signs + symptoms of folate deficiency
- Those relating to anaemia - pallor, tiredness, breathless
- reduced sense of taste
- diarrhoea
- numbness and tingling in feet and hands
- muscle weakness
- depression
What can be used to prevent neural tube defects in babies during pregnancy?
Folic acid before conception + during 1st 12 weeks of pregnancy
What benefit does folic acid have of taken during pregnancy?
Prevents neural tube defects
Uses of vitamin B12
- cofactor for DNA synthesis
- needed for normal erythropoiesis
- normal function + development of CNS
Good sources of vitamin B12
Meat
Fish
Milk
Cheese
Eggs
Yeast extract
Outline vitamin B12 absorption
- B12 binds to haptocorrin in stomach
- haptocorrin B12 complex digested by pancreatic proteases > B12 released
- B12 binds to intrinsic factor
- IF-B12 complex enters enterocytes in terminal ileum via receptor-mediated endocytosis
- binds to transcobalamin in blood + transported
Where is vit B12 stored?
How long does it last for?
Liver
3-6 years
Causes of vitamin B12 deficiency
- Poor diet - vegan diet lacks B12
- lack of intrinsic factor»_space; pernicious anaemia
- disease of ileum e.g. Crohn’s disease
- lack of transcobalamin
- chemical inactivation of B12
- parasitic infection»_space; can trap B12
Signs and symptoms of vitamin B12 deficiency
- those relating to anaemia - pallor, fatigue etc.
- glossitis
- mouth ulcers
- Paraesthesia
- irritability
- diarrhoea
What causes pernicious anaemia
Decreased or absent intrinsic factor»_space; progressive exhaustion of B12 reserves
What does folate deficiency in pregnancy cause?
Neural tube defects
Effect of B12 deficiency on nervous system
- Focal demyelination - B12 needed for myelin sheath production
- Reversible peripheral neuropathy - most common
- Subacute combined degeneration of cord - irreversible
What is subacute combined degeneration of the cord due to?
vit B12 deficiency
Symptoms of subacute combined degeneration of the cord
- Gradual onset weakness + Paraesthesia in arms, legs + trunk which gets worse
- Change in mental state
Link between B12 and folate
- B12 is needed for stable methyltetrahydrofolate to be converted to tetrahydrofolate
- lack of B12 prevents this + stops FH4 from being used in synthesis of thymidine for DNA synthesis
Why do B12 + folate deficiencies cause megaloblastic anaemia?
- cause a thymidine deficiency
- uracil is incorporated into DNA instead
- DNA repair enzymes detect the errors + constantly repair by excision
- results in nucleus not fully maturing as cytoplasm matures at normal rate > megaloblast > larger RBCs
Megaloblastic features in blood film
Tear drop RBCs
Anisopoikilocytosis - variance in size + shape
Ovalocytes
Hypersegmented neutrophils - >6 lobes more
Macrocytic RBCs
Treatment of folate deficiency
Oral folic acid
Treatment of vitamin B12 deficiency
- Due to pernicious anaemia - IM hydroxocobalamin (NOT ORAL - due to no intrinsic factor)
- Other causes - oral cyanocobalamine
How does the body excrete iron?
No mechanism for excreting iron
How is free iron toxic to cells?
Contributes to formation of free radicals
Two types of iron and their charges
What type does the body like + not like?
Ferrous iron 2+ - Likes
Ferric iron 3+ - Ick’ doesnt like
What does two things does dietary iron consist of?
Haem iron - Fe2+
Non haem iron - mixture of 2+ and 3+
What form of iron can be absorbed?
Ferrous Fe2+
Where is iron absorbed?
Duodenum
Jejunum
Outline dietary absorption of iron
reductase
- Fe3+ > Fe2+
- DMT1 takes up Fe2+ into enterocyte
- stored as ferritin in form of Fe3+
- ferroportin transports Fe2+ into bloodstream
hephaestin
Fe2+ > Fe3+
- Fe3+ binds to transferrin + transported around body
What has a negative influence on absorbing iron from food?
Why?
- Tannins - in tea
- Phytates e.g chapattis + pulses
- Fibre
- Antacids
- Can bind non haem iron in intestine > reduces absorption
What has a positive influence on absorbing iron from food?
Vitamin C + citrate
What is deficient in pernicious anaemia?
Intrinsic factor
What cells secrete intrinsic factor
Parietal cells
Action of hepcidin
Inhibits action of ferroportin
Fe2+ gets trapped in enterocyte
How is iron stored?
Soluble ferritin Fe3+
Insoluble haemosiderin
Outline cellular uptake of iron
- Fe3+ bound transferrin bind to transferrin receptor
- taken up by receptor mediated endocytosis at target cell
- Fe3+ > Fe2+
- Fe2+ transported to cytosol via DMT1
- Fe2+ stored as ferritin, exported by ferroportin or taken up by mitochondria for cytochrome enzymes
Control mechanisms to regulate iron absorption
- regulation of transporters
- regulation of receptors
- hepcidin
Where is hepcidin released from?
Stimulated by
Inhibited by
Liver
S - Increase in iron overload
I - high erythropoietic activity
Causes of iron deficiency
Poor diet
Malabsorption of iron
Bleeding
Increased requirement
Anaemia of chronic disease
Signs and symptoms of iron deficiency
- Fatigue
- Pallor
- Pica - unusual craving for non-nutritive substances e.g. ice, dirt
- cold peripheries
- epithelial changes - koilonychia
- angular cheilitis
Iron deficiency in blood film
Microcytic
Hypochromic
Anisopoikilocytosis
Sometimes pencil + target cells
How do you diagnose iron deficiency?
- Reduced plasma ferritin»_space; definitely indicates iron deficiency
- Normal or increases does not exclude iron deficiency as it can be increased due to other reasons
Treatment of iron deficiency
Dietary advice
Oral iron supplements - ferrous sulphate
IM iron injection
IV iron
FBC results in iron deficiency
Low MCV
Low ferretin, iron
Raised TIBC
Low CHr - reticulocyte haemoglobin content
What can excess iron cause?
What can cause excess iron?
- Deposited in organs as haemosiderin
- Promotes free radicals formation
. - transfusion associated haemosiderosis
- hereditary haemochromostosis
What is hereditary haemochromtosis?
- Autosomal recessive disease casued by mutation in HFE gene
- Normally promotes hepcidin + reduces transferrin receptor affinity
- Mutation in HFE gene doesnt allow this to happen
- causing too much iron to enter cells > accumulates in end organs > damage
Treatment of hereditary haemochromatosis
Venesection
What free radicals are made by excess iron?
What are is this reaction called?
Hydroxyl + hydroperoyl
Fenton reaction
Reasons for increased ferritin levels
Cancer
Infection
Inflammation
Liver disease
Alcoholism
Role of folate
- involved in synthesis of nucleotide bases needed for DNA + RNA synthesis
- provide carbons for other reactions
What is B12 produced by?
Bacteria
What needs to be considered when treating B12 deficiency in patients with pernicious anaemia?
- hydroxycobalamine
- drug NOT given orally: no intrinsic factor so B12 wouldn’t be absorbed
- hypokalaemia: due to increased K+ requirement as erythropoiesis increases
Dietary sources of haem iron
Liver
Kidney
Tuna
Salmon
Chicken
Beef
Pork
Dietary sources of non-haem iron
Potatoes
Rice
Oats
Beans
Fortified cereals
What is used to test for functional iron deficiency?
CHr
(reticulocyte haemoglobin content)
What is transfusion associated haemosiderosis?
- condition that occur when repeated blood transfusions are given
- causes iron levels to quickly build up
What can be used to help the effects of transfusion associated haemosiderosis?
Iron chelating agents
Delay NOT prevention
Risk groups for iron deficiency anaemia
- Menorrhagic women
- Infants being weaned off breast to solid foods
- women of child bearing age
- geriatric age group
What is given as an oral replacement for iron?
Ferrous sulphate
What two conditions can cause excess iron?
Transfusion associated haemosiderosis
Hereditary haemochromostosis
