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MEH > B12, Folate + Iron > Flashcards

B12, Folate + Iron Flashcards

1
Q

Where is folate synthesised in?

A

Bacteria + plants

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2
Q

Where is folate mainly absorbed from?

A

Duodenum
Jejunum

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3
Q

Outline the path of folate in the body

A
  • eaten
  • absorbed mainly from duodenum + jejunum
  • converted to tetrahydrofolate by intestinal cells
  • taken up by liver which acts as a store
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4
Q

Where is folate stored?
How long does it last?
How fast is it used up in anaemia?

A

Liver
3-4 months
Anaemia - 2 to 3 weeks

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5
Q

Causes of folate deficiency

A
  • 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
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6
Q

Signs + symptoms of folate deficiency

A
  • Those relating to anaemia - pallor, tiredness, breathless
  • reduced sense of taste
  • diarrhoea
  • numbness and tingling in feet and hands
  • muscle weakness
  • depression
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7
Q

What can be used to prevent neural tube defects in babies during pregnancy?

A

Folic acid before conception + during 1st 12 weeks of pregnancy

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8
Q

What benefit does folic acid have of taken during pregnancy?

A

Prevents neural tube defects

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9
Q

Uses of vitamin B12

A
  • cofactor for DNA synthesis
  • needed for normal erythropoiesis
  • normal function + development of CNS
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10
Q

Good sources of vitamin B12

A

Meat
Fish
Milk
Cheese
Eggs
Yeast extract

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11
Q

Outline vitamin B12 absorption

A
  • 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
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12
Q

Where is vit B12 stored?
How long does it last for?

A

Liver
3-6 years

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13
Q

Causes of vitamin B12 deficiency

A
  • Poor diet - vegan diet lacks B12
  • lack of intrinsic factor&raquo_space; pernicious anaemia
  • disease of ileum e.g. Crohn’s disease
  • lack of transcobalamin
  • chemical inactivation of B12
  • parasitic infection&raquo_space; can trap B12
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14
Q

Signs and symptoms of vitamin B12 deficiency

A
  • those relating to anaemia - pallor, fatigue etc.
  • glossitis
  • mouth ulcers
  • Paraesthesia
  • irritability
  • diarrhoea
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15
Q

What causes pernicious anaemia

A

Decreased or absent intrinsic factor&raquo_space; progressive exhaustion of B12 reserves

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16
Q

What does folate deficiency in pregnancy cause?

A

Neural tube defects

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17
Q

Effect of B12 deficiency on nervous system

A
  • Focal demyelination - B12 needed for myelin sheath production
  • Reversible peripheral neuropathy - most common
  • Subacute combined degeneration of cord - irreversible
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18
Q

What is subacute combined degeneration of the cord due to?

A

vit B12 deficiency

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19
Q

Symptoms of subacute combined degeneration of the cord

A
  • Gradual onset weakness + Paraesthesia in arms, legs + trunk which gets worse
  • Change in mental state
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20
Q

Link between B12 and folate

A
  • 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
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21
Q

Why do B12 + folate deficiencies cause megaloblastic anaemia?

A
  • 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
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22
Q

Megaloblastic features in blood film

A

Tear drop RBCs
Anisopoikilocytosis - variance in size + shape
Ovalocytes
Hypersegmented neutrophils - >6 lobes more
Macrocytic RBCs

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23
Q

Treatment of folate deficiency

A

Oral folic acid

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24
Q

Treatment of vitamin B12 deficiency

A
  • Due to pernicious anaemia - IM hydroxocobalamin (NOT ORAL - due to no intrinsic factor)
  • Other causes - oral cyanocobalamine
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25
Q

How does the body excrete iron?

A

No mechanism for excreting iron

26
Q

How is free iron toxic to cells?

A

Contributes to formation of free radicals

27
Q

Two types of iron and their charges
What type does the body like + not like?

A

Ferrous iron 2+ - Likes
Ferric iron 3+ - Ick’ doesnt like

28
Q

What does two things does dietary iron consist of?

A

Haem iron - Fe2+
Non haem iron - mixture of 2+ and 3+

29
Q

What form of iron can be absorbed?

A

Ferrous Fe2+

30
Q

Where is iron absorbed?

A

Duodenum
Jejunum

31
Q

Outline dietary absorption of iron

A

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

32
Q

What has a negative influence on absorbing iron from food?
Why?

A
  • Tannins - in tea
  • Phytates e.g chapattis + pulses
  • Fibre
  • Antacids
  • Can bind non haem iron in intestine > reduces absorption
33
Q

What has a positive influence on absorbing iron from food?

A

Vitamin C + citrate

34
Q

What is deficient in pernicious anaemia?

A

Intrinsic factor

35
Q

What cells secrete intrinsic factor

A

Parietal cells

36
Q

Action of hepcidin

A

Inhibits action of ferroportin
Fe2+ gets trapped in enterocyte

37
Q

How is iron stored?

A

Soluble ferritin Fe3+
Insoluble haemosiderin

38
Q

Outline cellular uptake of iron

A
  • 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
39
Q

Control mechanisms to regulate iron absorption

A
  • regulation of transporters
  • regulation of receptors
  • hepcidin
40
Q

Where is hepcidin released from?
Stimulated by
Inhibited by

A

Liver
S - Increase in iron overload
I - high erythropoietic activity

41
Q

Causes of iron deficiency

A

Poor diet
Malabsorption of iron
Bleeding
Increased requirement
Anaemia of chronic disease

42
Q

Signs and symptoms of iron deficiency

A
  • Fatigue
  • Pallor
  • Pica - unusual craving for non-nutritive substances e.g. ice, dirt
  • cold peripheries
  • epithelial changes - koilonychia
    - angular cheilitis
43
Q

Iron deficiency in blood film

A

Microcytic
Hypochromic
Anisopoikilocytosis
Sometimes pencil + target cells

44
Q

How do you diagnose iron deficiency?

A
  • Reduced plasma ferritin&raquo_space; definitely indicates iron deficiency
  • Normal or increases does not exclude iron deficiency as it can be increased due to other reasons
45
Q

Treatment of iron deficiency

A

Dietary advice
Oral iron supplements - ferrous sulphate
IM iron injection
IV iron

46
Q

FBC results in iron deficiency

A

Low MCV
Low ferretin, iron
Raised TIBC
Low CHr - reticulocyte haemoglobin content

47
Q

What can excess iron cause?
What can cause excess iron?

A
  • Deposited in organs as haemosiderin
  • Promotes free radicals formation
    .
  • transfusion associated haemosiderosis
  • hereditary haemochromostosis
48
Q

What is hereditary haemochromtosis?

A
  • 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
49
Q

Treatment of hereditary haemochromatosis

A

Venesection

50
Q

What free radicals are made by excess iron?
What are is this reaction called?

A

Hydroxyl + hydroperoyl
Fenton reaction

51
Q

Reasons for increased ferritin levels

A

Cancer
Infection
Inflammation
Liver disease
Alcoholism

52
Q

Role of folate

A
  • involved in synthesis of nucleotide bases needed for DNA + RNA synthesis
  • provide carbons for other reactions
53
Q

What is B12 produced by?

A

Bacteria

54
Q

What needs to be considered when treating B12 deficiency in patients with pernicious anaemia?

A
  • hydroxycobalamine
  • drug NOT given orally: no intrinsic factor so B12 wouldn’t be absorbed
  • hypokalaemia: due to increased K+ requirement as erythropoiesis increases
55
Q

Dietary sources of haem iron

A

Liver
Kidney
Tuna
Salmon
Chicken
Beef
Pork

56
Q

Dietary sources of non-haem iron

A

Potatoes
Rice
Oats
Beans
Fortified cereals

57
Q

What is used to test for functional iron deficiency?

A

CHr
(reticulocyte haemoglobin content)

58
Q

What is transfusion associated haemosiderosis?

A
  • condition that occur when repeated blood transfusions are given
  • causes iron levels to quickly build up
59
Q

What can be used to help the effects of transfusion associated haemosiderosis?

A

Iron chelating agents
Delay NOT prevention

60
Q

Risk groups for iron deficiency anaemia

A
  • Menorrhagic women
  • Infants being weaned off breast to solid foods
  • women of child bearing age
  • geriatric age group
61
Q

What is given as an oral replacement for iron?

A

Ferrous sulphate

62
Q

What two conditions can cause excess iron?

A

Transfusion associated haemosiderosis
Hereditary haemochromostosis

MEH (23 decks)

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