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MEH > Intro To Anaemia, B12 And Folate Metabolism And Megaloblastic Anaemia > Flashcards

Intro To Anaemia, B12 And Folate Metabolism And Megaloblastic Anaemia Flashcards

1
Q

Anaemia Definition

A

Haemoglobin concentration lower than the normal range

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2
Q

Clinical SIGNS of Anaemia

A

PALLOR
TACHYCARDIA
Tachypnoea (faster breathing)
SYSTOLIC MURMUR
Hypotension

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3
Q

Anaemia symptoms

A

Fatigue
Dyspnoea (shortness of breath)
Weakness and lethargy
Headaches
COnfusion

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4
Q

Anaemia is not a diagnosis

A

It’s a manifestation of an underlying disease state
Important to establish cause of anaemia

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5
Q

Anaemias can occur as a result of abnormalities in RBC what?

A

Production
Function
Removal
Excessive loss of blood

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6
Q

How are anaemias classified

A

Depends of how the underlying condition affects the average SIZE of the red cells

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7
Q

How many classifications of Anaemia

A

3

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8
Q

The 3 Anaemia Classifications

A

Macrocytic Anaemia (Large Cells)
Microcytic Anaemia (Small Cells)
Normocytic Anaemia (Average/Normal Cells)

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9
Q

Aplastic Anaemia

A

Reduced erythropoiesis due to Haematopoietic stem cells being unable to make RBCs

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10
Q

Common Cause of Aplastic Anaemia

A

Chronic Kidney Disease
Kidney make erythropoietin, low levels might not be enough to stimulate erythropoiesis

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11
Q

What is Megaloblastic anaemia?

A

Inability of precursor RBCs to synthesis DNA
Because of this cell constantly stuck in growth phase so cytoplasm increases in size
Asynchronous maturation between nucleus and cytoplasm

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12
Q

Which category of anaemia is Megaloblastic anaemia?

A

Macrocytic

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13
Q

Deficiency in which vitamins causes Megaloblastic anaemia?

A

Vitamin B12
Folate

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14
Q

Different causes of Microcytic Anaemia PNUEMONIC

A

TAILS

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15
Q

Different Causes of Microcytic Anaemia

A

T - Thalassaemia
A - Anaemia of chronic disease
I - Iron Deficiency
L - Lead poisoning
S - Sideroblastic anaemia

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16
Q

What is haem iron, what form is the iron in and how is it obtained?

A

Iron that is associated with a haem group
Ferrous form Fe2+
From animal sources

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17
Q

What is non-haem iron, what form is the iron in and how is it obtained?

A

Free iron not bound to a haem group
Ferrous (Fe2+) and Ferric form (Fe3+)
Animal and non animal sources (plants)

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18
Q

Good Haem Iron sources

A

Liver
Kidney
Chicken
Duck
Pork chop
Salmon/Tuna
Beef steak/burger

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19
Q

Good sources of non-haem iron

A

Beans
Raisins
Figs
Barley
Oats
Rice
Potatoes

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20
Q

How does Iron deficiency lead to anaemia

A

Iron is needed to synthesise haemoglobin since it is part of the haem group which transports oxygen in RBCs

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21
Q

Iron deficiency treatment

A

Dietary advice
Intramuscular iron injections
Oral Iron supplements (safest start point)
Intravenous iron

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22
Q

Folate stored where?

A

Liver

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23
Q

What is folate converted to and stored as in lIver?

A

Tetrahydrofolate (FH4)

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24
Q

General Role of Tetrahydrofolate (FH4)

A

Act as one carbon carrier
Provides carbons to other reactions

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25
Q

What is the One-Carbon pool

A

The wide variety of carbon forms of Tetrahydrofolate FH4

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26
Q

Key reactions which the carbons from Tetrahydrofolate are needed for

A

Synthesis of Thymidine (T base)
Synthesis of Adenine and Guanine (DNA and RNA Synthesis)

Transfer of methyl groups to Vitamin B12

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27
Q

Problem with Folate deficiency in pregnancy

A

Foetus can develop Neural Tube Defects

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28
Q

Type of Inheritance for Hereditary Haemochromatosis and what gene is affected?

A

Autosomal Recessive Inheritance
HFE Gene

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29
Q

WHat is Hereditary Haemochromatosis normally characterised by?

A

Excess absorption of Dietary Iron
HFE Gene stands for H = High Fe = Iron

THERE IS NO SYSTEM FOR EXCRETION OF EXCESS IRON

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30
Q

What does the normal protein for the affected gene in Hereditarty Haemochromatosis do?

A

Interacts with transferrin receptor
Reduces affinity for iron bound transferrin so less iron is taken into cells
Promotes Hepcidin production so Ferroportin internalised and degraded so less iron absorbed into blood

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31
Q

What do defects of the HFE Protein cause and why?

A

Increased cellular uptake of iron
Negative affect of iron uptake into cells lost (no HFE protein to reduce affinity of transferrin rreceptor)
No HFE protein means less Hepcidin so more absorption of Iron into blood since Ferroportin not internalised and degraded

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32
Q

Treatment of Hereditary Haemochromatosis

A

Therapeutic phlebotomy to remove excess iron (venesection)

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33
Q

Iron deficiency anaemia is what type of anaemia and why?

A

Microcytic
Less haemoglobin can be synthesised so cell are smaller and hypochromic (paler)

34
Q

What is an enterocyte?

A

A cell lining the intestines

35
Q

Where is iron absorbed?

A

In the intestines
Specifically the Duodenum and Jejunum

36
Q

How is haem iron absorbed into the Enterocyte?

A

Readily
Is absorbed as it is

37
Q

What happens to the haem iron in the enterocyte?

A

Enzyme removes the Ferrous Iron from it the haem group (Fe2+)
Fe2+ then oxidised to Ferric Iron (Fe3+) which is stored in the Ferritin complex OR Absorbed straight into the blood by travelling across another transporter

38
Q

What is Ferritin?

A

IRON STORAGE MOLECULE
It is a protein which stores Iron in the Ferric form (Fe3+)within the enterocyte

39
Q

How is NON-Haem Iron absorbed into the enterocyte?

A

Ferrous Iron (Fe2+) transported in by DMT1
Ferric Iron (Fe3+) reduced to Ferrous iron (Fe2+) by Ferrin REDUCTASE enzyme.
The Ferrous iron (Fe2+) thin enters enterocyte via DMT1

40
Q

What is DMT1?

A

Divalent Metal Transporter 1

Divalent = Only liking Fe2+ Ferrous iron
Not liking FerrICK iron, it gives it the ICK

41
Q

What donates the electron to Ferric iron so it can be reduced to Ferrous iron by the REDUCTASE enzyme?

A

Vitamin C

42
Q

Why is Vitamin C important in absorption of non haem iron?

A

Donates electron (e-) to Fe3+ so it can be reduced to Fe2+ so it can be absorbed into the enterocyte via the DMT1

43
Q

For non haem iron, what form of Iron does it need to be so it can be absorbed?

A

FERROUS IRON FE2+ !!!!

44
Q

What is Ferroportin?

A

The transporter protein that allows Iron to leave the Enterocyte into the blood in the Ferrous Form (Fe2+)

45
Q

What form must iron be in to be absorbed into the blood via Ferroportin?

A

Fe2+ = Ferrous Iron

46
Q

What is TRANSferrin?

A

The protein which allows Iron to be TRANSported around in the blood

47
Q

What form must Iron be in to be TRANSported by TRANSferrin?

A

Ferric Fe3+

48
Q

How is Ferrous iron that enters into the blood converted/oxidised into Ferric iron so that it can be transported by Transferrin?

A

By Protein Hephaestin

49
Q

Hephaestin function

A

Facilitates oxidation of Ferrous (Fe2+) into Ferric Iron (Fe3+) so iron can be TRANSported by TRANSferrin in the Blood

50
Q

What is Hepcidin?

A

A protein produced by the liver which internalises and degrades Ferroportin

51
Q

What does Hepcidin do?

A

Binds to Ferroportin causing it to be internalised into the enterocyte and degraded

52
Q

What is the significance of Hepcidin Internalising Ferroportin into the cell?

A

Iron becomes trapped into the Enterocyte so can’t enter the blood
This causes a lack of functional iron in the blood

53
Q

What other cells does Hepcidin affect besides the Enterocyte and how does it affect the cell?

A

Macrophages in the Reticuloendothelial system (RES)
Traps iron in them

54
Q

What 2 forms is Iron Stored in?

A

Ferritin (Soluble)
Haemosiderin (Insoluble)

55
Q

Haemosiderin consists of what?

A

Aggregates (a collection of clumped ferritin, denatured protein and lipids)

56
Q

Where does Haemosiderin accumulate?

A

In macrophages in liver (kupffer cells), spleen and bone marrow)

57
Q

Basic step by step of cell uptake of iron

A

Fe3+ bound transferrin binds to transferrin receptor
Receptor mediated endocytosis
Fe3+ ——> Fe2+
Leaves endosome via DMT1 into cytoplasm
Fe2+ either stored as ferritin,used by mitochondria or later transported out of cell via Ferroportin

58
Q

Why is excess iron dangerous?

A

NO system to remove excess iron from the body

59
Q

Mechanism on why iron in excess is dangerous

A

Iron promotes free radical production via the FENTON Reaction
Produces Hydroxyl (OH) and hydroperoxyl (OOH) radicals

60
Q

How do free radicals cause damage to cells?

A

Lipid peroxidation
Damage to proteins (cross linking)
Damage to DNA

61
Q

What is iron needed for in the body?

A

Proteins (Haemoglobin)
Cytochromes in ETC (why mitochondria take up iron)
Catalase enzyme (Protects from oxidative stress, breaks down H202)

62
Q

Why does the body only experience mild symptoms when anaemia develops slowly over a long period of time?

A

Body has time to adjust to lower [Hb]

Increased cardiac stroke volume

Increased levels of 2,3-bisphosphoglycerate in erythrocytes to promote oxygen dissociation (reduces Hb affinity for 02)

63
Q

Acute onset anaemia symptoms

A

Fatigue
Dyspnoea
Palpitations
Headaches
Angina

64
Q

Vitamin B12 source

A

Animal origin
Vegans need supplements

65
Q

Vitamin B12 absorption quick overview

A

B12 binds to haptocorrin
B12 haptocorrin complex digested by pancreatic proteases in small int
B12 binds to intrinsic factor
b12 - Intriinsic factor complex binds to Cubam receptor
Receptor mediated endocytosis into enterocyte
B12 moves into blood and binds to transcobalamin (transport protein)

66
Q

What causes vitamin B12 deficiency?

A

Lack of B12 in diet
Lack of Intrinsic factor (pernicious anaemia)
Disease of ileum (Chron’s disease)
Lack of transcobalamin (Transport of B12)
Chemical inactivation of B12

67
Q

Pernicious Anaemia

A

Lack of intrinsic factor causing reduced B12 absorption, often die to an autoimmune disease

68
Q

How are B12 and Folate linked

A

B12 needed in Methionine cycle (Methionine produces cysteine)
Methyltetrahydrofolate needed as cofactor for Methionine cycle to work
So lack of B12 causes lack of folate since it stays trapped as Methyltetrahydrofolate

69
Q

Simple link between B12 and folate

A

Low B12 causes low available Tetrahydrofolate
Methionine cycle ceases (low B12) so all Folate gets stuck as Tetrahydrofolate

70
Q

Subacute combined degeneration of the cord is caused by what

A

B12/Folate Deficiency

Where demyelination of the cord occurs due to lacking B12

71
Q

B12 is needed for myelin sheath production

A

AFfects nervous system

72
Q

Metabolic defects in RBCs that might cause anaemia

A

Glucose-6-Phosphate Dehydrogenase deficiency (G6PDH Deficiency)
Pyruvate Kinase deficiency

73
Q

Why would G6PDH Deficiency cause anaemia?

A

Pentose-Phosphate pathway can’t replenish NADPH
RBCs vulnerable to oxidative stress since GSH can’t be reduced to active form

Cross linking of inappropriate disulphide bonds between haemoglobin chains causes Heinz bodies to form
Leads to haemolysis

74
Q

Why would pyruvate kinase deficiency cause anaemia?

A

RBC dependant of Glycolysis for ATP (no mitochondria)
Glycolysis pathway defective
RBC can’t produce ATP
Haemolysis

75
Q

5 reasons why Iron deficiency anaemia might occur?

A

Increased blood loss
Increased requirements (pregnancy, growth spurt)
Decreased absorption
Anaemia of chronic disease (lack of functional iron)
Diet

76
Q

Anaemia of Chronic disease/inflammation occurs due to increased production of what?

A

Cytokines

77
Q

Cytokines do what to contribute to anaemia

A

Increased Hepcidin production (Liver) (affecting Ferroportin)
Macrophages retain iron, also less iron absorbed into the blood from gut

Inhibit Erythropoietin production by kidney inhibiting erythropoiesis
Cytokines also directly inhibit erthyropoiesis

78
Q

Macrocytic anaemia causes

A

Folate/B12 Deficiency (Megaloblastic anaemia)
Alcohol consumption (has antifolate effect)
Liver disease

79
Q

How do you treat pernicious anaemia?

A

Intramuscular injection of hydroxycobalamine

80
Q

What type of anaemia does Koilonychia and Angular Stomatitis suggest?

What does Koilonychia mean?

What does Angular Stomatitis mean?

A

Iron deficiency anaemia

Koilonychia = spoon shaped nails

Angular Stomatitis = inflammation of corners of mouth

81
Q

What is Glossitis?

What type of anaemia is this indicative of?

A

Inflammation and depapillation of tongue

Vit B12 deficiency

MEH (33 decks)

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