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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
What are NSAID?
Nonsteroidal anti-inflammatory drugs commonly used to treat pain and inflammation
26
What are 3 examples of NSAID?
Aspirin Ibuprofen Naproxen
27
What are 4 causes of chronic bleeding?
Heavy menstrual bleeding Repeated nosebleeds GI bleeding Kidney of bladder tumors
28
What is autoimmune haemolytic anaemia?
Autoantibodies bind to red cell membrane proteins causing them to be recognized by macrophages in spleen and destroyed
29
Why does splenomegaly occur in haemolytic anaemias?
Spleen doing extra work
30
What are 2 key features to work out the cause of anaemia?
Size | Presence or absence of reticulocytosis
31
What are reticulocytes?
Immature RBCs with no nucleus but have RNA, larger than RBCs
32
What is macrocytic anaemia?
Average RBC size is more than normal (MCV high)
33
What are 3 types of macrocytic anaemias?
Megaloblastic anaemia Macronormoblastic erythropoesis Stress erythropoiesis
34
What causes megaloblastic anaemias?
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
35
What is macronormoblastic erythropoiesis?
Normal relationship between development of nucleus and cytoplasm is retained but erythroblasts are larger than normal
36
What is stress erythropoiesis?
High reticulocyte count as high level of erythropoietin leads to expanded and accelerated erythropoiesis
37
How does the body get folate?
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
What does the body use folate for?
Provide carbons for other reactions like synthesis of nucleotide bases needed for DNA and RNA synthesis
39
What are 6 causes of folate deficiency?
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
What are 6 symptoms of folate deficiency?
``` Anaemia like symptoms Reduced sense of taste Diarrhea Numbness in feet and hands Muscle weakness Depression ```
41
When does folic acid need to be taken during pregnancy and why?
Taken before conception and during first 12 weeks of pregnancy prevents majority of neural tube defects in babies
42
Is vitamin B12 water or fat soluble?
Water
43
What are the 3 uses of vitamin B12?
Cofactor for DNA synthesis Erythropoiesis Function of CNS
44
Where can vitamin B12 be obtained from?
Animal products
45
How is vitamin B12 absorbed by the body?
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
What are the 7 causes of vitamin B12 deficiency?
``` Dietary deficiency Lack of intrinsic factor Diseases of ileum Lack of transcobalamin Chemical inactivation of B12 Parasitic infestation Drugs that chelate intrinsic factor ```
47
What is pernicious anaemia?
Decreased or absent intrinsic factor causes progressive exist on of B13 reserves
48
What are 6 symptoms of vitamin B12 deficiency?
``` Anaemia symptoms Glossitis and mouth ulcers Diarrhea Parasthesia Disturbed vision Irritability ```
49
What are 3 neurological impacts of B12 deficiency?
Focal demyelination Reversible peripheral neuropathy Subacute combined degeneration of cord
50
What is subacute combined degeneratiom of cord?
Degeneratiom of posterior and lateral columns of spinal cord
51
What are 3 symptoms of subacute combined degeneration of spinal cord?
Gradual onset weakness Numbness in limbs Changes in mental state
52
How will lack of B12 affect folate?
Traps folate in stable methyltetrahydrofolate form, preventing its use in other reactions like synthesis of thymidine for DNA synthesis
53
Why do B12 and folate deficiency lead to megaloblastic anaemia?
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
What are 5 features you would see in a megaloblastic blood film?
``` Anisopoikilocytosis Tear drop red cells Ovalocytes Hypersegmented neutrophils Macrocytic red cells ```
55
Why is plasma lactate dehydrogenase raised in megaloblastic anaemia?
Due to increased cell destruction and increased cell production
56
How to treat folate deficiency?
Oral folic acid
57
How to treat pernicious anaemia?
Hydroxycobalamine intramuscular injection for life
58
What is something to look out for when treating severe pernicious anaemia?
Hypokalaemia as there is increased K+ requirement as erythropoiesis increases back to its normal rate
59
How to treat other causes of B12 deficiency?
Oral cyanocobalamine
60
What is microcytic anaemia?
When erythrocytes are smaller than normal
61
What are the 2 main causes of microcytic anaemia?
Reduced haem synthesis | Reduced globin chain synthesis
62
What are 4 causes of reduced haem synthesis?
Iron deficiency Anaemia of chronic disease Lead poisoning Sideroblastic anaemia
63
What are 2 causes of reduced globin chain synthesis?
Alpha thalassaemia | Beta thalassaemia
64
What are the 2 roles of iron?
Oxygen carrier | Co factor in many enzymes
65
How does the body excrete iron?
No way
66
What form of iron is absorbed from diet?
Fe2+
67
How much iron do you need?
10-15mg/day
68
Where does absorption of iron occur?
Duodenum | Upper jejunum
69
What are 4 factors that reduce absorption of non-haem iron from food?
Tannins in tea Phytates Fibre Antacids
70
What are 2 factors that promote absorption of non-Haem from food?
Vitamin C | Citrate
71
What are the 2 forms of stored iron?
Ferritin | Haemosiderin
72
What is the difference between ferritin and haemosiderin?
Ferritin is soluble, haemosiderin is not
73
What are the 4 steps of taking up iron into cell?
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
How does hepcidin regulate iron absorption?
Hepcidin induces internalization and degradation of ferroportin, blocking iron transport
75
When is hepcidin synthesis increased?
Iron overload
76
When is hepcidin decreased?
High erythropoietic activity
77
What are 5 causes of iron deficiency?
``` Insufficient iron in diet Malabsorption of iron Bleeding Increased requirement Anaemia of chronic disease ```
78
What are 4 signs and symptoms of iron deficiency?
Anaemia effects Pica Cold hands and feet Epithelial changes
79
What are 3 forms of epithelial changes during iron deficiency?
Angular cheilitis Glossy tongue Koilonychia
80
What are ways to test for iron deficiency?
Reduced plasma ferritin | Low Reticulocyte haemoglobin content
81
What are 5 ways to treat iron deficiency?
``` Dietary advice Oral iron supplements Intramuscular ion injections Intravenous iron Blood transfusion ```
82
What happens when iron is in excess?
Iron exceeds binding capacity of transferrin and deposited in organs as haemosiderin. It promotes free radical formation and organ damage
83
What are 2 conditions that can be caused by iron excess?
Transfusion associated haemosiderin is | Hereditary haemochromostosis
84
How does transfusion associated haemosiderosis occur?
Repeated blood transfusions gives gradual accumulation of iron
85
How to treat transfusion associated haemosiderosis?
Iron chelating agents like desferrioxamine can delay but don’t stop inevitable effects of iron overload
86
What is hereditary haemochromarosis caused by?
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
What does HFE protein do?
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
How to treat hereditary haemochromatosis?
Venesection

Metabolism, Endocrinology and Haematology (8 decks)

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