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MD2002 Lucas > Haematopathology: Anaemias and Leukemias > Flashcards

Haematopathology: Anaemias and Leukemias Flashcards

1
Q

Identify the main contents of RBCs.

A

Haemoglobin

Enzymes for glycolysis

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2
Q

Describe the differentiation process occurring starting at multipotent haematopoietic stem cell.

A

Multipotent haematopoietic stem cell differentiates into either common lymphoid progenitor or common myeloid progenitor (= CFU-GEMM = colony forming unit granulocyte, erythroid, megakarocyte, macrophage).

A subset of CFU-GEMM differentiates into CFU-Erythroid committed cells (become RBCs) while others become granulocytes, megakarocytes, macrophages.

Common lymphoid progenitor cells differentiate to become lymphocytes.

Haematopoiesis occurs mainly in bone marrow but some occurs in blood and tissue

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3
Q

Define Haematopoiesis.

A

Production of blood cells and platelets.

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4
Q

Describe the events following differentiation of CFU-GEMM into CFU-Erythrocyte.

A
  • CFU-Erythrocytes are clustered around macrophages (which contain the iron needed in haeme, in ferritin stores).
  • These erythrocytes are stimulated by erythropoietin (from kidney, secreted in response to falling O2 levels in tissues) to make Hb
  • Nucleus extruded from cell- released into venous sinusoid
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5
Q

How many days are needed for RBCs to mature in the bone marrow ?

A

7 days

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6
Q

What is the period for which RBCs are considered reticulocytes ?

A

24 hours

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7
Q

What is the lifespan of a RBC ? What is the percentage of RBCs renewed per day ?

A

120 day

1%

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8
Q

How many fold can RBC production increase by in situations of need (bleed etc.) ?

A

x10-20

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9
Q

How many RBCs per l are there in circulation ? Consequently, how many RBCs per l are needed per hour ?

A

5x 10x12/l in circulation so 10x10 needed per hour!

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10
Q

What must the ratio of production to destruction of RBCs be to maintain Hb levels ?

A

Production=destruction

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11
Q

Define anaemia.

A

Low Hb

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12
Q

What are the basic possible causes of low Hb ?

A
  • Too few RBC

- Too much plasma (but too much plasma does not really ever happen)

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13
Q

What are some factors that reference Hb ranges depend on ?

A
  • Age

- Gender

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14
Q

Is anaemia inherited or acquired ?

A

May be either inherited or acquired

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15
Q

Identify the different possible defects resulting in inherited anaemia.

A

1) Hb problem (eg sickle cell disease or thalassaemia)
2) Membrane problem (eg spherocytosis)
3) RBC enzyme problem (eg pyruvate kinase deficiency)

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16
Q

Describe the basic features of sickle cell anaemia.

A

-Single base (and hence AA) substitution
-Hb polymersises in situations of low O2
and produces sickle cells (hence cell breaks
down very quickly, causing anaemia)

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17
Q

Describe the basic features of thalassaemia.

A
  • Hypochromic (pale) and microcytic (small in size) RBCs
  • Due to underproduction of alpha or beta chains
  • Becomes apparent in early childhood
  • Symptoms include massive expansion of marrow spaces (forehead etc.) + anaemia
18
Q

Describe the basic features of Pyruvate Kinase Deficiency

Anaemia.

A
  • Clinically haemolytic
  • Pyruvate Kinase is important for Krebs Cycle (otherwise unable to metabolise glucose beyond Pyruvate)
  • In the absence of Pyruvate Kinase, haemolysis occurs
19
Q

Describe the basic features of Spherocytosis.

A
  • Sphere shaped rather than bi-concave disc shaped
  • Visible due to pale area in the middle of bi-concave disc. In contrast, dense appearance in the middle of sphere shaped
  • Linked with shorter red cell survival
  • Due to abnormality of spectrin (protein which holds red cell membrane together)
20
Q

What are possible causes of acquired anaemia ?

A
  • Nutritional deficiency
  • Blood loss
  • Haemolysis
  • Marrow infiltration (eg. primary or secondary malignancy)
  • Aplastic anaemia (“bone marrow and the hematopoietic stem cells that reside there are damaged”)
  • Renal failure (leading to erythropoietin underproduction, less drive for marrow to produce red cells)
  • Anaemia of chronic disease
21
Q

Identify examples of anaemias resulting from a lack of building blocks.

A

1) IRON DEFICIENCY
- Poor intake in diet
- Poor absorption (e.g. due to Coeliac disease)
- Excessive loss (e.g. bowel/bladder/menstrual loss, Hookworms causing bowel blood loss)

2) FOLATE DEFICIENCY
- Poor intake in diet
- Poor absorption (e.g. due to Coeliac disease)
- Excessive utilisation (i.e. due to any condition (e.g. chronic haemolysis) with high demand for red cell production, since folic acid/folate used up for red cell production)

3) B12 deficiency
- Poor absorption (due to Pernicious Anaemia)
- Typically a macrocytic anaemia and later a pancytopenia (often bilirubin and LDH (Lactate dehydrogenase) raised)
- Disease of terminal ileum (e.g. Crohn’s disease) or disease of stomach/stomach surgery

22
Q

What is the biggest cause of anaemia worldwide ?

A

Iron deficiency

23
Q

Where do we get B12 from ?

A

B12 is derived from animals and animal products

24
Q

What are some possible causes of haemolysis ?

A
  1. Autoimmune reasons
  2. Pyruvate Kinase deficiency
25
Q

Describe the process of auto-immune haemolysis.

A
  • Antibody produced directed against RBC membrane antigens
  • FC portion recognised by macrophages in spleen
  • Loss of membrane and shortened RBC survival. As a result, cells turn into spheres, which then pop
  • Treated with steroids / splenectomy / rituximab
26
Q

Explain the process of aplastic anaemia.

A
  • Basically, underproduction of blood.
  • Marrow turns empty and more fatty, resulting in decline of all cell productions (becomes 90% fat with little islands of marrow cells, when it should be 50:50)
  • It is a predictable dose related side effect of chemotherapy/radiation
  • Also an idiosyncratic side effect of chloramphenicol
  • Idiopathic, do not know why becomes aplastic
27
Q

Identify possible causes of marrow infiltration which may result in anaemia. How do they cause anaemia ?

A
  • Myeloma (cancer arising from plasma cells)
  • Leukaemia (cancer developing from leukocytes)
  • Lymphoma (cancers developing from lymphocytes)
  • Metastatic tumour (secondary malignancy)

By occupying space in the marrow, thus crowding out red cell production (and possibly causing a fracture).

28
Q

Explain how renal failure may lead to anaemia.

A

Lack of erythropoietin production leads to less drive for marrow to produce red cells.

29
Q

Explain how anaemia of chronic disease arises.

A

Typically a normocytic anaemia associated with chronic inflammatory disease

Plentiful iron stores but poor transfer to RBC due to hepcidin and cytokines

almost as common as iron deficiency

30
Q

Define the symptoms, age groups, FBC findings, progression, and genetic features of chronic myeloid leukemia.

A

-Symptoms of anaemia, large spleen (resulting in distended abdomens), bone pain, angina in older patients
-Occurs in all age groups
-Anaemia, high WBC and platelet count
-Typically a chronic phase (4-5 years) and then accelerated and blast phase (very short survival).
-95% of cases have an identical cytogenetic and molecular mutation
-Reciprocal translocation between chromosome 9 and 22. Material of long arm of chromosome 9 is swapped for material on long arm of chromosome 22.
End up with switch of material between two chromosomes leading to shorter chromosome 22 (and longer chromosome 9) + juxtaposition of BCR gene with ABL gene (BCR gene was already on chromosome 22 but ABL gene was originally on chromosome 9) on chromosome 22)
-Translocated chromosome 22 = Philadelphia chromosome (with juxtaposition of BCR gene with ABL gene)

31
Q

Describe the treatment for CML.

A

IMATINIB (=Gleevec)

  • (BCR-ABL?) code for tyrosine kinase enzyme which phosphorylates proteins to active them
  • In CML, massive activation through phosphorylation
  • If block kinase site competitively by Imatinib on bcr-abl tyrosine kinase enzyme, that stops substrate being phosphorylated and activated
  • Since pretty much everyone has same mutation, drug effective to most of the affected population
  • Treatment well tolerated (once a day oral medication)
  • Effect monitored (by measuring percentage of bcr-abl product in the cells)
  • Drug resistance unusual

INTERFERON

CHEMOTHERAPY

32
Q

What is the overall survival rate after 5 years for CML with the different treatment options ?

A 
Imatinib = 90%
Interferon = 60%
Chemo = 45%
33
Q

Define symptoms, age groups, histological findings, progression, and genetic features of acute myeloid leukemia.

A
  • More common with increasing age
  • Become ill within period of days-weeks
  • Presents with symptoms of marrow failure including anaemia, bleeding, infections (gross expansion of malignant WBCs means production of normal WBC affected, hence more vulnerable to infections)
  • Other symptoms include angina, shortness of breath
  • Histologically, increased presence of (large) B cells, and presence of Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of myeloid leukemic blasts)
  • Diverse cytogenetic changes so no single target for chemotherapy
34
Q

Describe the treatment for AML.

A

CHEMOTHERAPY

  • To produce marrow aplasia
  • Rely on ability of marrow to regenerate from residual stem cells (rely on ability of residual stem cells to grow back better than remaining leukaemic cells)
  • Whole process take 4 to 5 weeks, beginning to end (the treatment or the illness ?)
35
Q

What is the biggest factor in determining outcome in AML ?

A

Cytogenetic profile

36
Q

What are problems associated with chemotherapy treatment in AML ?

A
  • Infections (Not so much from other people. Instead, bugs in normal microbiota become more invasive as a result of chemo)
  • Bleeding (Due to underproduced platelets as a result of chemotherapy. E.g. distended retinal vessels and retinal haemorrhage)
  • Psychological (Due to staying in hospital)
  • Venous access (Relying on veins in hands and arms is a problem because need lots of blood samples, transfusions, antibiotics, chemotherapy. Hence, commonly use semi-permanent into jugular or subclavian vein)
37
Q

Who of CML or AML patients have a better prognostic ?

A

Those with CML (for all age categories)

38
Q

Why do older people affected by AML tend to also have poorer long term survival than the young affected by AML ?

A

Because:

a) Not so fit
b) Poorer cytogenetic changes

39
Q

Has newer treatment for ACL made any difference in the survival rates ? If so, what has contributed to this ?

A

Yes (but still lower survival rate than those treated with Imatinib for CML)

The increase in survival rate is thanks to patient support, better chemo, better selection of
patients (targeting certain patient groups with certain drugs according to particular disease
categories)

40
Q

B12 deficiency- treatment

A

Hydroxocobalamin 1mg intra-
muscular alternate days for 5
doses then 3 monthly if confirmed
ongoing need eg pernicious
anaemia

Cyanocobalamin orally used as
supplement eg on vegan diet

MD2002 Lucas (111 decks)

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