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Metabolism, Endocrinology and Haematology > Session 4 - Anaemia, B12 And Folate Metabolism, Megaloblastic Anaemia, Iron Metabolism And Microcytotic Anaemia > Flashcards

Session 4 - Anaemia, B12 And Folate Metabolism, Megaloblastic Anaemia, Iron Metabolism And Microcytotic Anaemia Flashcards

1
Q

What is the definition of anaemia?

A

Haemoglobin concentration lower than the normal range

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2
Q

What are 7 symptoms of anaemia?

A 
Shortness of breath
Palpitations
Headaches
Claudication 
Angina
Weakness
Confusion
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3
Q

What are 5 signs of anaemia?

A 
Pallor
Tachycardia
Systolic flow murmur
Tachypnoea
Hypotension
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4
Q

What is koilonychia?

A

Spoon shaped nails

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5
Q

What is angular stomatitis?

A

Inflammation of corners of mouth

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6
Q

What is glossitis?

A

Inflammation and depapillation of tongue

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7
Q

What does koilonychia suggest about the cause of anaemia?

A

Iron deficiency

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8
Q

What does angular stomatitis suggest about the cause of anaemia?

A

Iron deficiency

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9
Q

What does glossitis suggest about cause of anaemia?

A

Vitamin B12 deficiency

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10
Q

What does abnormal facial bone development suggest about the cause of anaemia

A

Thalassemia

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11
Q

What are 8 possible causes for development of anaemia?

A 
Reduced or dysfunctional erythropoiesis
Abnormal haem synthesis
Abnormal globin chain synthesis
Abnormal structure
Mechanical damage
Abnormal metabolism
Excessive bleeding
Increased removal by reticuloendothelial system
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12
Q

What is the role of erythropoietin in controlling erythropoiesis?

A

When there is low blood oxygen, pericytes in kidney senses hypoxia and produces erythropoietin, in the blood stream and binds to erythroblasts in bone marrow and stimulates red cell production, increased red cells in blood

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13
Q

What are 5 ways that erythropoiesis is reduced or dysfunctional?

A

Kidney stops making EPO - chronic kidney disease
Marrow cannot respond to EPO - chemotherapy
Marrow makes less cells - myelofibrosis
Iron is insufficient so cannot make red cells
Marrow stem cells abnormal - myelodysplastic syndromes

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14
Q

What are 3 ways that causes defects in haemoglobin synthesis?

A

Defects in haem synthetic pathway
Iron deficiency
Mutations in genes coding the globin chain proteins

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15
Q

What is sideroblastic anaemia?

A

Defects in haem synthetic pathway

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16
Q

What are 3 diseases that is caused by mutations in genes encoding the globin chain proteins?

A

Alpha thalassemia
Beta thalassemia
Sickle cell disease

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17
Q

What are 2 ways that will result in haemolytic anaemia?

A

Inherited

Acquired damage

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18
Q

How can haemolytic anaemia be inherited?

A

Mutations in genes coding for proteins involved in interactions between membrane and cytoskeleton causes cell to be less flexible and more easily damaged which makes them break up in circulation or removed by RES

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19
Q

What are 3 ways that causes acquired damage to red cells and causes anaemia?

A

Microangiopathic haemolytic anaemia from mechanical damage
Heat damage
Osmotic damage

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20
Q

What are 2 ways that cause mechanical damage and lead to microangiopathic haemolytic anaemia?

A

Shear stress as cells pass through a defective heart valve

Cells snagging on fibrin strands in small vessels

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21
Q

What are 2 defects in red cell metabolism that causes anaemia?

A

G6PDH deficiency

Pyruvate kinase deficiency

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22
Q

How does G6PDH deficiency cause anaemia?

A

Decreased G6PDH activity limits amount of NADPH, so oxidized GSSG cannot be reduced to GSH, less protection against oxidative stress, so damages proteins and haemoglobin cross links and form Heinz bodies which are recognized and removed

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23
Q

How does pyruvate kinase deficiency cause anaemia?

A

Glycolysis cannot occur and RBC has not ATP as it relies on glycolysis due to absent mitochondria so they undergo haemolysis

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24
Q

What are 3 ways that cause excessive bleeding?

A

Acute blood loss
Chronic NSAID usage
Chronic bleeding

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25
Q

What are NSAID?

A

Nonsteroidal anti-inflammatory drugs commonly used to treat pain and inflammation

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26
Q

What are 3 examples of NSAID?

A

Aspirin
Ibuprofen
Naproxen

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27
Q

What are 4 causes of chronic bleeding?

A

Heavy menstrual bleeding
Repeated nosebleeds
GI bleeding
Kidney of bladder tumors

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28
Q

What is autoimmune haemolytic anaemia?

A

Autoantibodies bind to red cell membrane proteins causing them to be recognized by macrophages in spleen and destroyed

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29
Q

Why does splenomegaly occur in haemolytic anaemias?

A

Spleen doing extra work

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30
Q

What are 2 key features to work out the cause of anaemia?

A

Size

Presence or absence of reticulocytosis

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31
Q

What are reticulocytes?

A

Immature RBCs with no nucleus but have RNA, larger than RBCs

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32
Q

What is macrocytic anaemia?

A

Average RBC size is more than normal (MCV high)

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33
Q

What are 3 types of macrocytic anaemias?

A

Megaloblastic anaemia
Macronormoblastic erythropoesis
Stress erythropoiesis

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34
Q

What causes megaloblastic anaemias?

A

Interference with DNA synthesis during erythropoiesis causes development of nucleus to be retarded compared to maturation of nucleus, so cell division is delayed and erythroblasts continue to grow to form megaloblasts

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35
Q

What is macronormoblastic erythropoiesis?

A

Normal relationship between development of nucleus and cytoplasm is retained but erythroblasts are larger than normal

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36
Q

What is stress erythropoiesis?

A

High reticulocyte count as high level of erythropoietin leads to expanded and accelerated erythropoiesis

37
Q

How does the body get folate?

A

Eating animal and vegetable food sources, absorbed from duodenum and jejunum, converted to tetrahydrofolate, which is then taken up by liver which acts like a store

38
Q

What does the body use folate for?

A

Provide carbons for other reactions like synthesis of nucleotide bases needed for DNA and RNA synthesis

39
Q

What are 6 causes of folate deficiency?

A

Dietary deficiency
Increased requirements
Disease of duodenum and jejunum
Drugs inhibiting dihydrofolate reductase
Alcoholism damaging intestinal cells
Urinary loss of folate in liver disease and heart failure

40
Q

What are 6 symptoms of folate deficiency?

A 
Anaemia like symptoms 
Reduced sense of taste
Diarrhea 
Numbness in feet and hands 
Muscle weakness 
Depression
41
Q

When does folic acid need to be taken during pregnancy and why?

A

Taken before conception and during first 12 weeks of pregnancy prevents majority of neural tube defects in babies

42
Q

Is vitamin B12 water or fat soluble?

A

Water

43
Q

What are the 3 uses of vitamin B12?

A

Cofactor for DNA synthesis
Erythropoiesis
Function of CNS

44
Q

Where can vitamin B12 be obtained from?

A

Animal products

45
Q

How is vitamin B12 absorbed by the body?

A

B12 released by proteolysis in stomach and binds to haptocorrin
Haptocorrin B12 complex digested by pancreatic proteases in small intestine, releases B12 which binds to intrinsic factor
Intrinsic factor - B12 complex binds to cubam receptor which mediates up take of complex by receptor mediated endocytosis into enterocytes
B12 exits via basolateral membrane through MDR1
Binds to transcobalamin in in blood and transported around bloodstream

46
Q

What are the 7 causes of vitamin B12 deficiency?

A 
Dietary deficiency 
Lack of intrinsic factor 
Diseases of ileum 
Lack of transcobalamin 
Chemical inactivation of B12 
Parasitic infestation
Drugs that chelate intrinsic factor
47
Q

What is pernicious anaemia?

A

Decreased or absent intrinsic factor causes progressive exist on of B13 reserves

48
Q

What are 6 symptoms of vitamin B12 deficiency?

A 
Anaemia symptoms 
Glossitis and mouth ulcers
Diarrhea 
Parasthesia
Disturbed vision 
Irritability
49
Q

What are 3 neurological impacts of B12 deficiency?

A

Focal demyelination
Reversible peripheral neuropathy
Subacute combined degeneration of cord

50
Q

What is subacute combined degeneratiom of cord?

A

Degeneratiom of posterior and lateral columns of spinal cord

51
Q

What are 3 symptoms of subacute combined degeneration of spinal cord?

A

Gradual onset weakness
Numbness in limbs
Changes in mental state

52
Q

How will lack of B12 affect folate?

A

Traps folate in stable methyltetrahydrofolate form, preventing its use in other reactions like synthesis of thymidine for DNA synthesis

53
Q

Why do B12 and folate deficiency lead to megaloblastic anaemia?

A

Lead to thymidine deficiency, so uracil is incorporated into DNA instead, DNA repair enzymes detect and constantly repairs, resulting in asynchronous maturation between nucleus and cytoplasm, so cytoplasm maturing but nucleus doesn’t mature so cannot divide, leading to large red cell precursors with inappropriately large nuclei and pennchromatin

54
Q

What are 5 features you would see in a megaloblastic blood film?

A 
Anisopoikilocytosis
Tear drop red cells 
Ovalocytes
Hypersegmented neutrophils 
Macrocytic red cells
55
Q

Why is plasma lactate dehydrogenase raised in megaloblastic anaemia?

A

Due to increased cell destruction and increased cell production

56
Q

How to treat folate deficiency?

A

Oral folic acid

57
Q

How to treat pernicious anaemia?

A

Hydroxycobalamine intramuscular injection for life

58
Q

What is something to look out for when treating severe pernicious anaemia?

A

Hypokalaemia as there is increased K+ requirement as erythropoiesis increases back to its normal rate

59
Q

How to treat other causes of B12 deficiency?

A

Oral cyanocobalamine

60
Q

What is microcytic anaemia?

A

When erythrocytes are smaller than normal

61
Q

What are the 2 main causes of microcytic anaemia?

A

Reduced haem synthesis

Reduced globin chain synthesis

62
Q

What are 4 causes of reduced haem synthesis?

A

Iron deficiency
Anaemia of chronic disease
Lead poisoning
Sideroblastic anaemia

63
Q

What are 2 causes of reduced globin chain synthesis?

A

Alpha thalassaemia

Beta thalassaemia

64
Q

What are the 2 roles of iron?

A

Oxygen carrier

Co factor in many enzymes

65
Q

How does the body excrete iron?

A

No way

66
Q

What form of iron is absorbed from diet?

A

Fe2+

67
Q

How much iron do you need?

A

10-15mg/day

68
Q

Where does absorption of iron occur?

A

Duodenum

Upper jejunum

69
Q

What are 4 factors that reduce absorption of non-haem iron from food?

A

Tannins in tea
Phytates
Fibre
Antacids

70
Q

What are 2 factors that promote absorption of non-Haem from food?

A

Vitamin C

Citrate

71
Q

What are the 2 forms of stored iron?

A

Ferritin

Haemosiderin

72
Q

What is the difference between ferritin and haemosiderin?

A

Ferritin is soluble, haemosiderin is not

73
Q

What are the 4 steps of taking up iron into cell?

A

Fe3+ bound transferrin binds to transferrin receptor and enters via receptor-mediated endocytosis
Fe3+ is reduced to Fe2+ in endoscope
Fe2+ is transported to cytosol via DMT1
Fe2+ can be stored in ferritin, exported by ferroportin, or taken up by mitochondria

74
Q

How does hepcidin regulate iron absorption?

A

Hepcidin induces internalization and degradation of ferroportin, blocking iron transport

75
Q

When is hepcidin synthesis increased?

A

Iron overload

76
Q

When is hepcidin decreased?

A

High erythropoietic activity

77
Q

What are 5 causes of iron deficiency?

A 
Insufficient iron in diet
Malabsorption of iron 
Bleeding 
Increased requirement 
Anaemia of chronic disease
78
Q

What are 4 signs and symptoms of iron deficiency?

A

Anaemia effects
Pica
Cold hands and feet
Epithelial changes

79
Q

What are 3 forms of epithelial changes during iron deficiency?

A

Angular cheilitis
Glossy tongue
Koilonychia

80
Q

What are ways to test for iron deficiency?

A

Reduced plasma ferritin

Low Reticulocyte haemoglobin content

81
Q

What are 5 ways to treat iron deficiency?

A 
Dietary advice
Oral iron supplements
Intramuscular ion injections 
Intravenous iron 
Blood transfusion
82
Q

What happens when iron is in excess?

A

Iron exceeds binding capacity of transferrin and deposited in organs as haemosiderin. It promotes free radical formation and organ damage

83
Q

What are 2 conditions that can be caused by iron excess?

A

Transfusion associated haemosiderin is

Hereditary haemochromostosis

84
Q

How does transfusion associated haemosiderosis occur?

A

Repeated blood transfusions gives gradual accumulation of iron

85
Q

How to treat transfusion associated haemosiderosis?

A

Iron chelating agents like desferrioxamine can delay but don’t stop inevitable effects of iron overload

86
Q

What is hereditary haemochromarosis caused by?

A

Mutation in HFE gene, loses negative influences on iron uptake and absorption, too much iron enters cells and accumulates in end organs causing damage

87
Q

What does HFE protein do?

A

Interacts with transferrin receptor to reduce affinity for iron bound transferrin and promotes hepcidin expression through activation of signalling pathways, negatively influencing iron uptake and absorption

88
Q

How to treat hereditary haemochromatosis?

A

Venesection

Metabolism, Endocrinology and Haematology (8 decks)

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