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5. Anaemia Flashcards

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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
Which GI disease could lead to decreased IF-B12 absorption in the ileum?
Crohn's
26
Why can B12 deficiency take a long time to develop compared to folate deficiency?
B12 can be stored for years in the body, whereas folate cannot be stored for long.
27
Which part of the GI tract is responsible for folate absorption?
Duodenum and jejunum
28
Dietary folate is converted to _________ , which circulates in the plasma.
Methyltetrahydrofolate (MethylTHF)
29
Errors in which 3 things can lead to folate deficiency?
1. Folate levels - dietary deficiency or increased use 2. Decreased absorption in duodenum and jejunum - crohn's, coeliac 3. Dihydrofolate reductase inhibited
30
How does methotrexate lead to folate deficiency?
Inhibits enzymes dihydrofolate reductase which converts folate to Methyl THF.
31
In what situations might increased use of folate be causing a deficiency?
Pregnancy Increased erythropoiesis - haemolytic anaemia Severe skin disease - psoriasis
32
What would you see on a blood film from a patient with folate or B12 deficiency?
Macrocytic red cells Hypersegmented neutrophils (>5 lobes) Pancytopenia can develop as it progresses
33
As well as anaemia, B12 deficiency is associated with which other type of disease?
Neurological - causes demyelination affecting spinal sort, peripheral nerves and optic nerves. Depression and dementia can develop
34
What mutation is responsible for causing sickle cell anaemia, what is it's inheritance pattern?
Point mutation - Glu6Val in beta globin chain | Autosomal recessive
35
What clinical problems can sickle cell anaemia cause?
Vaso-occlusion - small capillaries blocked by misshapen cells Aplastic - bone marrow Haemolytic
36
What structural change happens in sickled cells which increases risk of thrombosis?
Hydrophobic pocket is formed, tetramers polymerise in deoxygenated state and sickle. This leads to thrombosis in small vessels.
37
Which organs are particularly affected by sickle cell thrombi?
Spleen microvasculature - infarct Lung capillaries - infarct Brain - stroke
38
What would you see in a blood film from a patient with thalassaemia?
Hypochromic (low Hb levels) | Microcytic
39
Why does splenomegaly and hepatomegaly secondary to thalassamia?
Liver and spleen undergo metaplasia to compensate for low erythrocyte numbers (extra medullary haematopoiesis)
40
Why can patients get skeletal abnormalities in thalassaemia?
Expansion of haematopoiesis into the bone cortex
41
What is a major cause of premature death in patients with thalassaemia?
Iron overload due to excessive iron absorption as ineffective haematopoiesis.
42
What would you see in a blood film from patients with thalassaemia?
Target cells, hypochromic, microcytic, nucleated RBC's
43
What is hydrops fatalis?
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
What is the commonest inherited form of anaemia as a result of cell membrane defects?
Hereditary spherocytosis
45
What conditions can lead to acquired damage to red cell membranes and anaemia, how can you diagnosis this from a blood film?
Heart valves - endocarditis, stenosis Vasculitis DIC Broken fragments visible on blood film
46
Enzyme defects in which 2 key enzymes lead to anaemia?
Pyruvate kinase | G6PDH
47
Other than anaemia, what can acute blood loss lead to?
Hypovolaemic shock
48
Chronic blood loss may be invisible to the naked eye and be the cause anaemia. How can it present on a blood film?
Microcytic, development of iron deficient state - any unexplained microcytic anaemia needs investigating!!
49
What type of anaemia may present with schistocytes on a blood film?
Haemolytic anaemia - fragments of cells visible.
50
What causes autoimmune haemolytic anaemia?
Autoantibodies against proteins on red cell membranes leads to increased destruction by spleen and splenomegaly.
51
What are the key laboratory features of autoimmune haemolytic anaemia?
Raised reticulocytes Raised bilirubin Raised LDH (enzyme present in red cells)
52
What test can be used to detect presence of autoantibodies bound to RBC's?
Coombs test
53
What shaped red cells would you see in a patient with myelofibrosis?
Tear drop shaped - as squeezed out
54
Which myeloproliferative disorders can lead to overproduction of blood cells?
1. Essential thrombocythaemia 2. Polycythaemia vera 3. Myelofibrosis All dysregulation at HPSC
55
What are the clinical features of overproduction of blood components?
Hypercellular marrow/fibrosis Cytogenetic abnormalities Thrombosis/ haemorrhagic Extramedullary haematopoiesis
56
What is polycythaemia vera and its clinical complications?
Increased production of red cells. Increased haematocrit increases stickiness of blood leading to thrombosis.
57
Point mutation of which tyrosine kinase often causes increased proliferation of blood cells.
JAK2
58
How is PCV managed?
Venesection to reduce haematocrit | Aspirin
59
Which anaemia's are microcytic?
Thalassaemia ACD (can be both) Iron deficiency
60
What is the bodies physiological response to anaemia?
Increased 2,3-BPG concentration to encourage oxygen delivery
61
Define anaemia.
A haemoglobin concentration lower than the normal range.
62
What is a sign of intravascular haemolysis, why does it occur?
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
Hereditary spherocytosis changes causes a loss in which key property of RBC's?
Flexibility lost- become rigid. Spherocytes haemolyze as they pass through the small diameter blood vessels of the spleen.
64
What is a schistocyte and when are they seen?
A fragmented part of a red blood cell, seen in haemolytic anaemia.
65
How would you expect reticulocyte count to change in anaemia, how can this be a diagnostic indicator?
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
True or false: Patients who are haemolysing need regular folate replacement .
True - body cannot store for long.
67
True or false: A low Vitamin B12 level can be the cause of sideroblastic anaemia.
False. Can be caused by B6.
68
True or false: A normal ferritin level excludes iron deficiency anaemia.
False - A low ferritin level indicates iron deficiency but a normal or high level does not exclude it
69
When are blister cells typically seen on a blood film?
G6PDH deficiency
70
What do spherocytes look like on a blood film?
Lack central pale region that normal biconcave RBCs have.
71
What mode of inheritance does hereditary spherocytosis display?
Autosomal dominant
72
What would you see on the blood film from a patient with iron deficiency anaemia?
Microcytic, hypochromic
73
What happens in anaemia of chronic disease?
Increase hepcidin synthesis Erythroid production in marrow inhibited Inhibits EPO release

MEH (19 decks)

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