Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Semester 2 - MEH > 10. When Haemopoiesis goes wrong > Flashcards

10. When Haemopoiesis goes wrong Flashcards

1
Q

What are myeloproliferative neoplasms?

A

A group of diseases of the bone marrow in which excess cells are produced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do myeloproliferative neoplasms arise?

A

Genetic mutations in the precursors of the myeloid lineage in the bone marrow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the 4 major types of MPNs?

A
  1. Polycythaemia vera (excess erythrocytes)
  2. Essential thrombocythaemia (overproduction of megakaryocytes leading to excess platelets)
  3. Primary myelofibrosis (initial proliferative phase followed by replacement of haematopoietic tissue by connective tissue leading to impairment of the generation of all blood cells (pancytopenia))
  4. Chronic myeloid leukaemia (excess granulocytes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is polycythaemia?

A

Polycythaemia is a disease state in which the volume percent of erythrocytes in the blood (the haematocrit) exceeds 52% (males) or 48% (females).
This disease state can either be absolute or relative.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is absolute and relative polycythaemia?

A

Absolute: increase in the number erythrocytes
Relative: decrease in the plasma volume

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Explain what polycythaemia Vera is

A

This is a specific type of polycythaemia, it arises from a myeloproliferative neoplasm (tumour) in the bone marrow, this results in an overproduction of erythrocytes.
In some cases white blood cells and platelets can also be overproduced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are most cases of PCV caused by?

A

95% caused by mutation of the gene coding for Janus Kinase 2 (JAK2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is JAK2 and what is its normal function?

A

Cytoplasmic tyrosine kinase whose normal function is to stimulate signalling pathways leading to erythrocyte production in response to the hormone erythropoietin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What occurs in cells with mutated JAK2?

A

Multipotent stem cells harbouring the JAK2 mutation survive longer and proliferate continuously.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the clinical features of PCV as a result of?

A

Blood being thicker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the clinical features of PCV?

A
  • Thrombosis (venous & arterial)
  • Haemorrhage (skin or GI tract)
  • Headache and ‘dizziness’
  • Plethora (excess of bodily fluid)
  • Burning pain in the hands or feet(Erythromelalgia)
  • Pruritus (itching)
  • Splenic discomfort, splenomegaly
  • Gout
  • Arthritis
  • May transform to myelofibrosis or acute leukaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are treatments for PCV?

A
  • phlebotomy to maintain the haematocrit below 45%.
  • Aspirin due to its anti-platelet effects may be prescribed unless contraindicated
  • cytoreduction using agents such as hydroxycarbamide (oral antimetabolite that inhibits DNA synthesis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When might cytoreduction using agents be used to treat PCV?

A

Should be considered if the patient has poor tolerance of venesection, shows symptomatic or progressive splenomegaly or other evidence of
disease progression, e.g. weight loss and night sweats.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the 2 divisions of absolute polycythaemia?

A

Primary: myoproliferative neoplasm (abnormality originates in bone marrow) (PCV only example)

Secondary: caused by increased levels of EPO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the clinical features of myeloproliferative disorders?

A
  • Overproduction of one or several blood elements with dominance of a transformed clone.
  • Hypercellular marrow / marrow fibrosis.
  • Cytogenetic abnormalities.
  • Thrombotic and/or haemorrhagic diatheses.
  • Extramedullary haemopoiesis (liver/spleen).
  • Potential to transform to acute leukaemia.
  • Overlapping clinical features.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the two types of secondary absolute polycythaemia?

A

physiological response to hypoxia

pathological - abnormal production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are physiological causes of increased EPO?

A

Central hypoxia: chronic lung disease (COPD), R to L shunts, high altitudes, CO poisoning etc.

Renal hypoxia: renal artery stenosis, polycystic disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are pathological causes of increased EPO?

A
  • hepatocellular carcinoma
  • renal cell cancer
  • cerebellar haemangioblastoma
  • uterine tumours
  • phaeochromocytoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is thrombocytosis?

A

an increase in the platelet count compared to the normal range of a person of the same gender and age.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What can cause thrombocytosis?

A

It can be as a result of a reaction to an infection or inflammation. It can also be due to a myeloproliferative neoplasm (essential thrombocythaemia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is primary thrombocytosis?

A

abnormality originates in bone marrow - myeproliferative neoplasm

called ESSENTIAL THROMBOCYTHAEMIA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is secondary thrombocytosis?

A

Normal bone marrow response to extrinsic stimulus (e.g. infection, inflammation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is redistributional thrombocytosis?

A

Platelets redistributed from the splenic pool into the blood stream (e.g. in hyposplenism or after splenectomy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Explain what essential thrombocythaemia is

A

This is a rare and chronic blood cancer that can be identified by an overproduction of platelets by megakaryocytes In the bone marrow.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How are the megakaryocytes different in essential thrombocythaemia?

A

Larger than normal and in excess.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What causes essential thrombocythaemia?

A
  • Half the cases are caused by JAK2 mutations
  • also by mutation in calreticulin gene (CALR)
  • mutations in thrombopoietin receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is CALR and what is its normal function?

A

Produces a protein called calreticulin:
a multifunctional soluble protein that binds Ca2+ ions (a second messenger in signal transduction), rendering it inactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the most common symptoms of essential thromboycthaemia?

A
  • Numbness in the extremities
  • Thrombosis (most often arterial e.g. stroke or peripheral gangrene)
  • Disturbances in hearing and vision (related to microvascular complications)
  • Headaches
  • Burning pain in the hands or feet(Erythromelalgia)
29
Q

How are essential thrombocythaemic patients classified and what is it based on?

A

Patients are typically classified as low and high risk for bleeding/blood clotting (based on age, medical history, blood count and lifestyle) and treated accordingly

30
Q

What are the factors of a high risk essential thrombocythaemic patient?

A

> 60 years, platelet count >1500 or disease-related

thrombosis/haemorrhageq

31
Q

How are low risk thrombocythaemic patients treated?

A

Usually treated with aspirin

32
Q

How are high risk thrombocythaemic patients treated?

A

Aspirin and also given hydroxycarbamide and/or other treatments that reduce platelet count

33
Q

What is Thrombocytopenia?

A

It’s a condition characterised by an abnormally low level of platelets.

34
Q

What are the 2 categories of thrombocytopaenia?

A

Acquired (common)

Inherited (rare syndromes)

35
Q

Which conditions cause inherited thrombocytopaenia?

A

Fanconi anaemia, Bernard-Soulier

syndrome (associated with large platelets) and Alport syndrome

36
Q

When do symptoms of thrombocytopaenia occur?

A

Patients generally not symptomatic until the platelet count < 30

37
Q

What are symptoms of thrombocytopaenia?

A
  • mucosal bleeding: nosebleeds, gums
  • women may have heavier or longer menstrual periods.
  • spontaneous bleeding under the skin: bruising and petechiae/pupura
  • severe bleeding after trauma
  • intracranial haemorrhage
38
Q

What are petechiae and purpura?

A

Petechiae: a small red or purple spot caused by bleeding into the skin (smaller than pupura)

Purpura: a rash of purple spots on the skin caused by internal bleeding from small blood vessels

39
Q

What can acquired thrombocytopaenia arise from?

A
  • decrease in platelet production
  • increased consumption of platelets (e.g. due to DIC)
  • increased destruction of platelets.
40
Q

What factors cause decrease in production of platelets?

A
  • B12 or folate deficiency
  • acute leukaemia or aplastic anaemia
  • liver failure (decreased produciton in thrombopoietin)
  • sepsis
  • cytotoxic chemotherapy
41
Q

What factors cause increase consumption of platelets?

A
  • massive haemorrhage
  • disseminated intravascular coagulation
  • thrombotic thrombocytopaenic purpura
42
Q

What factors cause increase destruction of platelets?

A
  • (auto)immune thrombocytopaenic purpura
  • drug induced (e.g. heparin)
  • hypersplenism (increase destruction and splenic pooling of platelets)
43
Q

How is Acquired thrombocytopenia typically detected?

A

from a full blood count

44
Q

How is thrombocytopenia treated?

A

Treatment depends on the specific cause of the disease and focuses on eliminating the underlying problem (e.g. discontinuing a drug or treating underlying sepsis).

45
Q

What is immune thrombocytopaenia purpura?

A

Autoimmune disease characterised by isolated thrombocytopenia which can take an acute (short-lived) or chronic course. It presents due to symptoms if the platelet count is very low or as an incidental finding on a blood count.

46
Q

What causes the thrombocytopaenia in ITP?

A

Mainly anti-platelet autoantibodies

T-cell activity against the platelets and megakaryocytes are contributory

47
Q

Which molecules do antibodies target in ITP

A

Autoantibodies against Glycoproteins on platelets:

- GPIIb/IIIa and GPIb/IX

48
Q

What commonly causes ITP in children?

A

nfection

- associated with a better outcome with often spontaneous improvement in the platelet count and no relapse

49
Q

What is ITP associated with in adults?

A

Autoimmune diseases:
- rheumatoid arthritis or systemic lupus erythematosus (SLE)

Underlying lymphoid cancers:
- lymphoma or leukaemia

HIV

No obvious cause is found in 80% of adult cases

50
Q

Give a complication that can arise as a result of ITP

A

No obvious cause is found in 80% of adult cases

51
Q

What are the treatments for ITP?

A
  • immunosuppressive drugs (e.g. corticosterioids)
  • intravenous pooled human Immunoglobulin
  • splenectomy
  • more recently thrombopoietin receptor agonists.
52
Q

What is Primary myelofibrosis?

A

Primary myelofibrosis is a myeloproliferative neoplasm where the proliferation of mutated hematopoietic stem cells results in reactive bone marrow fibrosis eventually leading to the replacement of marrow with scar tissue (collagen deposition).

53
Q

How does extramedullary haemopoiesis occur in primary myelofibrosis?

A

Mobilisation of mutated progenitor cells from bone marrow can also occur and these cells can colonise the liver and spleen. For this reason patients with primary myelofibrosis often show an enlarged liver and spleen.

54
Q

Mutations in which protein is associated with myelofibrosis?

A

JAK2

55
Q

What is secondary myelofibrosis?

A

Disease has developed as a consequence of polycythaemia vera or essential thrombocythaemia.

56
Q

What are the symptoms of myelofibrosis?

A
  • Massive Hepatosplenomegaly
  • Portal hypertension
  • Bruising
  • Fatigue (and other symptoms related to anaemia)
  • Weight loss (splenomegaly, compression on stomach)
  • Fever
  • Increased sweating
57
Q

What are the treatments for myelofibrosis?

A

Mainly supportive:

  • Hydroxycarbamide
  • folic acid
  • allopurinol may have some benefits.

Patients with advance disease may require:

  • blood transfusions
  • sometimes splenectomy.

Recently the drug ruxolitinib

58
Q

What is ruxolitinib?

A

An inhibitor of JAK2 has been shown to significantly reduce spleen volume and improve symptoms of myelofibrosis

59
Q

What may FBCs of chronic myeloproliferative neoplasms show?

A

Progressive pancytopaenia

- due to to bone marrow fibrosis and hypersplenism

60
Q

Differentiate between acute and chronic leukaemia

A

the best way to think about the types of leukaemia is whether they are ‘acute’ or ‘chronic’ and what lineage do the abnormal clonal malignant cells arise from.

Acute leukaemias rapidly cause bone marrow failure due to large numbers of immature blast cells overwhelming the ability of the tissue to produce mature blood cells.

Chronic leukaemias are more often slow to cause symptoms and may even be picked up as a chance finding on a blood count. In chronic leukaemias (in contrast to acute leukaemia) there is often differentiation i.e. the malignant clonal cell may be a mature cell, as in the commonest leukaemia B-CLL (chronic lymphocytic leukaemia).

61
Q

What is chronic myeloid leukaemia?

A

Characterized by the unregulated growth of myeloid cells in the bone marrow leading to the accumulation of mature granulocytes (mainly neutrophils) as well as myelocytes in blood

62
Q

What is CML caused by?

A

Chromosomal translocation called the Philadelphia chromosome involving a reciprocal translocation
between chromosomes 9 and 22
- This translocation causes an oncogenic gene fusion (BCR-ABL)

63
Q

What does BCR-ABL code for?

A

tyrosine kinase activity that results in proliferation, differentiation and inhibition of apoptosis.

64
Q

What is used to treat CML?

A

targeted cancer therapy through drugs which inhibit the ATP-binding site of the tyrosine kinase
- e.g. imatinib

65
Q

What is aplastic anaemia?

A

Rare disease resulting in damage to bone marrow

and hematopoietic stem cells leading to pancytopenia

66
Q

What is pancytopenia?

A

a deficiency of all three blood cell types: red blood cells (anaemia), white blood cells (leucopenia), and platelets (thrombocytopenia)

67
Q

What does the term aplastic refer to?

A

simply refers to an inability of the stem cells to generate mature blood cells.

68
Q

What can cause aplastic anaemia?

A

genetic causes, auto immunity or exposure to chemicals, drugs, or radiation.

Semester 2 - MEH (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions