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MEH > 5. Anaemia > Flashcards

5. Anaemia Flashcards

1
Q

What 3 conditions could lead to decreased erythropoiesis?

A
  1. Chronic Kidney disease - EPO production low
  2. Empty bone marrow - can’t respond to EPO
  3. Marrow infiltrated by cancer cells or fibrous tissue
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2
Q

How can you treat anaemia of kidney disease?

A

Recombinant EPO given

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3
Q

When might bone marrow be ‘empty’ and unable to respond to EPO?

A

After chemotherapy, aplastic anaemic, toxic insult - parvovirus

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4
Q

What is myelofibrosis and how do it cause anaemia?

A

Marrow infiltrated by fibrous tissue, decreased erythropoiesis as fewer space for heamatopoietic cells.

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5
Q

What are 2 causes of dyserythropoiesis?

A
  1. Anaemia of chronic disease

2. Myelodysplastic syndromes

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6
Q

What conditions might you expect to see ACD?

A

RA, UC, Crohn’s, chronic infections - TB

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7
Q

How does chronic inflammation affect erythropoiesis?

A

Inflammation increases Hepcidin synthesis, inhibiting iron release, causing a lack of functional iron.

  • reduced life span of cells
  • marrow lack of response to EPO
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8
Q

What blood test results would support a diagnosis of anaemia of chronic disease?

A

Raised CRP as well as raised ferritin

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9
Q

What would you see on a blood film from a patient with ACD?

A

Can be microcytic, macrocytic or normocytic

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10
Q

How would you expect red blood cells to appear on blood film from a patient with myelodysplasia, why?

A

Macrocytic - cells do not mature properly so are large and abnormal

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11
Q

Why does myelodysplasia lead to anaemia and possibly pancytopaenia?

A

Defective cells are prematurely destroyed by RES.

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12
Q

How is myelodysplasia treated?

A

Chronic transfusions of red cells

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13
Q

Why does myelodysplasia usually occur in elderly patients, what cancer can it develop to?

A

Due to genetic changes in the chromosomes of marrow cells, it can lead to acute leukaemia.

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14
Q

What are 3 forms of haemoglobin abnormalities?

A
  1. Iron deficiency
  2. Deficiency in DNA building blocks - folate, B12
  3. Mutations in globin genes - thalassaemia, sickle cell
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15
Q

What is the name given to anaemia as a result of B12 or folate deficiency?

A

Megaloblastic anaemia

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16
Q

What would you see in a blood film of a patient with megaloblastic anaemia?

A

Macrocytic cells with large nuclei.

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17
Q

What would you see in the bone marrow of a patient with megaloblastic anaemia?

A

More cells and less fat spaces (should be 50:50)

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18
Q

Before being absorbed in the GI tract, what is B12 combined with?

A

Glycoprotein intrinsic factor (IF) to form IF-B12 complex

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19
Q

Which cells produce the glycoprotein intrinsic factor?

A

Parietal cells

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20
Q

What plasma protein binds to Vit B12 in the portal blood?

A

Transcobalamin - delivers B12 to bone marrow and other tissues

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21
Q

Where is the IF-B12 complex absorbed?

A

Ileum - IF is destroyed and B12 is absorbed.

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22
Q

Deficiency in B12 could be due to defects in which 4 things?

A
  1. Dietary deficiency
  2. Intrinsic factor deficiency
  3. Decreased absorption
  4. Trancobalamin deficiency - congenital
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23
Q

What is the name given to anaemia due to IF deficiency?

A

Pernicious anaemia

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24
Q

What could cause pernicious anaemia?

A

Autoimmune conditions affecting gastric parietal cells, gastrectomy, atrophic gastritis.

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25
Q

Which GI disease could lead to decreased IF-B12 absorption in the ileum?

A

Crohn’s

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26
Q

Why can B12 deficiency take a long time to develop compared to folate deficiency?

A

B12 can be stored for years in the body, whereas folate cannot be stored for long.

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27
Q

Which part of the GI tract is responsible for folate absorption?

A

Duodenum and jejunum

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28
Q

Dietary folate is converted to _________ , which circulates in the plasma.

A

Methyltetrahydrofolate (MethylTHF)

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29
Q

Errors in which 3 things can lead to folate deficiency?

A
  1. Folate levels - dietary deficiency or increased use
  2. Decreased absorption in duodenum and jejunum - crohn’s, coeliac
  3. Dihydrofolate reductase inhibited
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30
Q

How does methotrexate lead to folate deficiency?

A

Inhibits enzymes dihydrofolate reductase which converts folate to Methyl THF.

31
Q

In what situations might increased use of folate be causing a deficiency?

A

Pregnancy
Increased erythropoiesis - haemolytic anaemia
Severe skin disease - psoriasis

32
Q

What would you see on a blood film from a patient with folate or B12 deficiency?

A

Macrocytic red cells
Hypersegmented neutrophils (>5 lobes)
Pancytopenia can develop as it progresses

33
Q

As well as anaemia, B12 deficiency is associated with which other type of disease?

A

Neurological - causes demyelination affecting spinal sort, peripheral nerves and optic nerves.
Depression and dementia can develop

34
Q

What mutation is responsible for causing sickle cell anaemia, what is it’s inheritance pattern?

A

Point mutation - Glu6Val in beta globin chain

Autosomal recessive

35
Q

What clinical problems can sickle cell anaemia cause?

A

Vaso-occlusion - small capillaries blocked by misshapen cells
Aplastic - bone marrow
Haemolytic

36
Q

What structural change happens in sickled cells which increases risk of thrombosis?

A

Hydrophobic pocket is formed, tetramers polymerise in deoxygenated state and sickle. This leads to thrombosis in small vessels.

37
Q

Which organs are particularly affected by sickle cell thrombi?

A

Spleen microvasculature - infarct
Lung capillaries - infarct
Brain - stroke

38
Q

What would you see in a blood film from a patient with thalassaemia?

A

Hypochromic (low Hb levels)

Microcytic

39
Q

Why does splenomegaly and hepatomegaly secondary to thalassamia?

A

Liver and spleen undergo metaplasia to compensate for low erythrocyte numbers (extra medullary haematopoiesis)

40
Q

Why can patients get skeletal abnormalities in thalassaemia?

A

Expansion of haematopoiesis into the bone cortex

41
Q

What is a major cause of premature death in patients with thalassaemia?

A

Iron overload due to excessive iron absorption as ineffective haematopoiesis.

42
Q

What would you see in a blood film from patients with thalassaemia?

A

Target cells, hypochromic, microcytic, nucleated RBC’s

43
Q

What is hydrops fatalis?

A

Severe form of alpha thalassaemia where all 4 alpha globin genes are deleted. Gamma globin form tetramers in foetus but these are unable to deliver oxygen.
Intrauterine death.

44
Q

What is the commonest inherited form of anaemia as a result of cell membrane defects?

A

Hereditary spherocytosis

45
Q

What conditions can lead to acquired damage to red cell membranes and anaemia, how can you diagnosis this from a blood film?

A

Heart valves - endocarditis, stenosis
Vasculitis
DIC
Broken fragments visible on blood film

46
Q

Enzyme defects in which 2 key enzymes lead to anaemia?

A

Pyruvate kinase

G6PDH

47
Q

Other than anaemia, what can acute blood loss lead to?

A

Hypovolaemic shock

48
Q

Chronic blood loss may be invisible to the naked eye and be the cause anaemia. How can it present on a blood film?

A

Microcytic, development of iron deficient state - any unexplained microcytic anaemia needs investigating!!

49
Q

What type of anaemia may present with schistocytes on a blood film?

A

Haemolytic anaemia - fragments of cells visible.

50
Q

What causes autoimmune haemolytic anaemia?

A

Autoantibodies against proteins on red cell membranes leads to increased destruction by spleen and splenomegaly.

51
Q

What are the key laboratory features of autoimmune haemolytic anaemia?

A

Raised reticulocytes
Raised bilirubin
Raised LDH (enzyme present in red cells)

52
Q

What test can be used to detect presence of autoantibodies bound to RBC’s?

A

Coombs test

53
Q

What shaped red cells would you see in a patient with myelofibrosis?

A

Tear drop shaped - as squeezed out

54
Q

Which myeloproliferative disorders can lead to overproduction of blood cells?

A
  1. Essential thrombocythaemia
  2. Polycythaemia vera
  3. Myelofibrosis
    All dysregulation at HPSC
55
Q

What are the clinical features of overproduction of blood components?

A

Hypercellular marrow/fibrosis
Cytogenetic abnormalities
Thrombosis/ haemorrhagic
Extramedullary haematopoiesis

56
Q

What is polycythaemia vera and its clinical complications?

A

Increased production of red cells. Increased haematocrit increases stickiness of blood leading to thrombosis.

57
Q

Point mutation of which tyrosine kinase often causes increased proliferation of blood cells.

A

JAK2

58
Q

How is PCV managed?

A

Venesection to reduce haematocrit

Aspirin

59
Q

Which anaemia’s are microcytic?

A

Thalassaemia
ACD (can be both)
Iron deficiency

60
Q

What is the bodies physiological response to anaemia?

A

Increased 2,3-BPG concentration to encourage oxygen delivery

61
Q

Define anaemia.

A

A haemoglobin concentration lower than the normal range.

62
Q

What is a sign of intravascular haemolysis, why does it occur?

A

Haemoglobinaemia - excess haemoglobin in the blood. If the RES overwhelmed, a direct breakdown of red blood cells rusults in release of haemoglobin into the circulation.

63
Q

Hereditary spherocytosis changes causes a loss in which key property of RBC’s?

A

Flexibility lost- become rigid. Spherocytes haemolyze as they pass through the small diameter blood vessels of the spleen.

64
Q

What is a schistocyte and when are they seen?

A

A fragmented part of a red blood cell, seen in haemolytic anaemia.

65
Q

How would you expect reticulocyte count to change in anaemia, how can this be a diagnostic indicator?

A

Increase to increase production of red blood cells. If reticulocyte levels are normal it suggests lack of materials to make RBC’s - iron deficiency or ACD.

66
Q

True or false: Patients who are haemolysing need regular folate replacement .

A

True - body cannot store for long.

67
Q

True or false: A low Vitamin B12 level can be the cause of sideroblastic anaemia.

A

False. Can be caused by B6.

68
Q

True or false: A normal ferritin level excludes iron deficiency anaemia.

A

False - A low ferritin level indicates iron deficiency but a normal or high level does not exclude it

69
Q

When are blister cells typically seen on a blood film?

A

G6PDH deficiency

70
Q

What do spherocytes look like on a blood film?

A

Lack central pale region that normal biconcave RBCs have.

71
Q

What mode of inheritance does hereditary spherocytosis display?

A

Autosomal dominant

72
Q

What would you see on the blood film from a patient with iron deficiency anaemia?

A

Microcytic, hypochromic

73
Q

What happens in anaemia of chronic disease?

A

Increase hepcidin synthesis
Erythroid production in marrow inhibited
Inhibits EPO release

MEH (19 decks)

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