Haem 6 Flashcards by Robert Grogan

Differentiate normal and malignant haemopoiesis

Normal:
Polyclonal healthy/reactive

Malignant
Abnormal/clonal
Leukaemia (lymphoid,myeloid), myelodysplasia , myeloproliferative

How well did you know this?

Not at all

Perfectly

Outline precursors to T cell, b cell, RBC, megakaryocyte/platelt, neutrophils, basophils, eosinophils and monocytes

Pre T, pre B, BFU-E, Meg-CFC, GM-CFC (granulocytes and monocytes),

CFC= colonony forming cells
BFU- E = erythroid burst-forming units

How well did you know this?

Not at all

Perfectly

How to differntiate myeloblast and lymphoblast

Myeloblast small granues, nothing in lymphoblast

How well did you know this?

Not at all

Perfectly

Outline the differentiaton of myeloblast into a neutrophil

Myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –>band cell –> neutrophil

How well did you know this?

Not at all

Perfectly

When would you see any myeloid precurosrs, not just neutrophils

In a myeloproliferative disease, e.g. chronic myeloid leukaemia incl. myeloblast

After chemotherapy when G-CSF given to increase formation of new granulocytes so lots of blasts in peripohery)

Sepsis (up to promyelocyte)

How well did you know this?

Not at all

Perfectly

How is cell number controlled in productin of erythroid, lymphoid and myeloid cells

Haemopoiesis regulated by cytokines, chemokines and hormone…..

(so in infection, cytokines released could message the bone marrow that more neturophils required)

Erythroid- erythropoietin
Lymphoid- IL2
Myeloid- G-CSF and M-CSF (just monocyte)

Influence DIFFERENTIATION and PROLIFERATION

DNA directed differentiation and proliferation

How well did you know this?

Not at all

Perfectly

Cell types found in bone marrow

Lymphoblasts

Myelpblast,promyeloblast,melocyte, metamyelocyte

How well did you know this?

Not at all

Perfectly

How could WBC increase

Increase cell production:
Reactive (infection or inflammation)
Malignant (leukaemia or myeloproliferative)

Increase cell survival (failure of apoptosis –> acquired cancer causing mutations in lymphomas)

How well did you know this?

Not at all

Perfectly

How could WBC decrease

Decreased cell production (impaired BM function, due to b12/folate deficiency OR BM failure- apalstic anaemia, post chemo, metastatic cancer, haematological cancer)

Decreased cell survival (immune breakdown e.g. HIV)

How well did you know this?

Not at all

Perfectly

Examples of normal (or reactive) with primary (malignant) haemopoiesis

Normal haemopoiesis:

Inflammation,
infection (parasitic),
increased cytokine production from distant tumour, (haemopoietc or non haemopoietic)

Abnormal haemopoiesis:

cancer of haemopoietic cells,
leukaemia (myeloid/lymphoid, chronic or acute)
myeloproliferative disorder

How well did you know this?

Not at all

Perfectly

Genetic basis of CML

Fusion gene called BCR-ABL due to translocation of chromosome 9 and 22…

DNA damage occurs at early stage of differenation (at GM-CFC) so it leads to proliferation of many myeloid cell types (platelets, all white cells, etc)

How well did you know this?

Not at all

Perfectly

How is a raised WCC investigated

CHECK

BASICALLY: 
History and examination
Haemoglobin and platelet count 
Automated differential
Examine blood film

History and examination

Haemoglobin and platelet count (if low, could be because the immature cells produced in acute lymphoid leukaemia, for example, are suppressing platelet and red cell production because there are so many)

Automated differential (machine tells you about each type of blood cell….could be no differential if there are lots of blasts….. there could be lots of blasts because of malignancy OR because patient has been treated with G-CSF following chemotherapy to increase white cell count)

Examine blood film

Abnormality White cells only, or all 3 lineages (red cells/platelets/white cells)…. in malignancy usually only increase in ONE cell lineage, in reactivity increase in all the white cells (apart from CML, which also has all cells prolferating)

White cells 1 cell type only, or all white cell lineages? (e.g. neuts/eos/monocytes/lymphocytes)

Mature cells only or mature and immature cells?

How well did you know this?

Not at all

Perfectly

Causes of elevated WCC with:

increased by mature cells

increased mature +immature

Immatuure

Mature:

all lineages or only 1 of neutrophil, eos or baso –> reactive/infection
lymphocytes –> reactive (viral) or primary (chronic lymphocytic leukaemia)

Mature and immature: 
Neutrophils+
myelocytes+
basophils
?Chronic myeloid 
leukaemia

Immature: 
Blasts +
low Hb
low platelets
? Acute leukaemia

How well did you know this?

Not at all

Perfectly

Neutrophil life span

2-3 days

How well did you know this?

Not at all

Perfectly

T/F: neutrophils that are marginated are included in FBC

False

How well did you know this?

Not at all

Perfectly

Cuase of neutrophilia which develops in minutes, hours, and days

mins: demargination (i.e. neutrophils stop going into tissues)
hours: early release from BM
days: increased production (X3 in inection)

How well did you know this?

Not at all

Perfectly

How do neutrophils change in infection and CML

Study These Flashcards

infectin: Neutrophilia >7.5x109/l
toxic granulation
vacuoles

CML: Neutrophilia (mature) and precursor cells (myelocytes), increase in monotcytes too… neutrophils don’t have toxic granules

Common causes of neutrophilia

Study These Flashcards

Tissue inflammation (e.g.colitis, pancreatitis)
Physical stress, adrenaline, CORTICOSTEROIDS
Underlying neoplasia
ie. Malignant neutrophilia:
- myeloproliferative disorders like CML

SIN: Stress, inflammation, neoplasia

Cuases of neutrophilia in infection

Study These Flashcards

in localised and systemic acute bacterial, fungal, certain viral infections (less so)

Which infections will not have neutrophilia

Study These Flashcards

brucella, typhoid, many viral infections.

Causes of eosinophilia

Study These Flashcards

-Reactive (parasitic infection; allergic disease e.g. asthma, rheumatoid, polyartertitis, pulmonary eosinopholia);
- neoplasms inc. Hodgkin’s or T cell NHL;
- hypereosinopshilic syndrome

Malignant:
Only one cause involing clonal process= Malignant chrnoic eosinopholic leukaemia (PDGFR fusion gene… fusion between FIP1L1 and PDGFR-a)

When is monocytosis seen

Study These Flashcards

Chronic infections and primary haematological disorders.

TB, brucella, typhoid
Viral; CMV, varicella zoster
Sarcoidosis
Chronic myelomonocytic leukaemia

Causes of mature lymphocytosis

Study These Flashcards

Mature

reactive to infection (EBV, CMV, toxoplasma),
autoimmune or inflammatory, sarcoidosis
underlying malignancy

primary disorder (CLL)

What is glandular fever

Study These Flashcards

EBV infection of B-lymphocytes via CD21 receptor
Infected B-cell proliferates and expresses EBV associated antigens
Cytotoxic T-lymphocyte response
acute infection resolved resulting in lifelong sub-clinical infection.

Infectious mononucleosis, atypical cells

What is more dangeorus monomorphic or pleomorphic lymphoytosis

monomorphic --> malignancy (clonal) Pleomorphic --> reactive

How can you distinguish between polyclonal and monoclonal lymphotcytosis

Immunophenotye (the antigens on the b cell surface)... in CLL they are CD5+

State the cells in the myeloid lineage

``` Monocyte Erythrocyte Dendritic cell Megakaryocyte Eosinophil Basophil Neutrophil Macrophage ```

How can there be a loss of regulation of haemopoiesis

Normally controlled by homones etc and is DNA directed after this. If DNA mutation at any point during differentiation, cells get survival advantage, stops being regulated by cytokines, replicates uncontrollable --> cancer.

Define leukaemia

Malignant disease, when bone marrow produce increased number of immature (in the case of proliferative disorders) /abnormal (in the case of dysplastic disorders) leuocytes, leading to suppression of production of other blood cells like erythrocytes, granulocytes and platelets. Can be myeloid or lymphoid

Define lymphoma

Lymphoma typically more solid and found in lymph nodes etc Leukaemia more often resulting in the increase of white cell count in the blood

Differentiate reactive increase in whicte cell production vs malignant one with regard to the bone marrow

Normal infection (IE. reactive) --> differentiating cells in bone marrow stimulated and mature cells released into ciructilation Hamatopoietic cancer (i.e. malignant), immature and mature cells released from the bone marrow

Difference in white cell count with malignancy and reactive haemopoiesis

In maliginacy, usually just one white cell type increased as clonal process, whereas reactive usually all cell types increased (exception is CML, in which all granulocytes increased and monocytes too)

Why is it important to see whether the increased WCC has mature white cells only or mature and immature cells

Mature and immature --> CML Immature only- AML

When might basophils be increased

Pox virus

How would CLL vs ALL look on microscope

CLL- mature cells.... all have characteristic large nucleus and small cytoplasm as in typical lymphocytes.. all look same. Remember, may also look like this in autoimmune ALL- much bigger, may contain nucleolus

What type of infections could cause reactive lymphocytosis

EBV, CMV, toxoplasma Infectious hep, rubella or herpes

How to distinguish cause of lymphocytosis (e.g. is it reactive to underlying autoimmune disorder or CLL?)

- Morphology (i.e. do they all look the same, if so CLL) - Immunophenotype (i.e. what surface molecules are they expressing, CLL ar CD5+) - Gene re-arrangement (if they are all derived from the same mother cell, they will have same TCR/immunoglobulin gene rearrangement, if they are different they will have different rearragnements.... use southern blot).... also use light chain (if all they are polyclonal, there will be a mixture of kappa only and lamda only lymphocytes..... in monoclonal, thus CLL, they will all be kappa or all be lamda)

What is aplastic anaemia

When there is damage to HSC so reduction in all cell types

Differentiate myelodysplastic and myeloproliferative disease

Myelodysplastic is when cells cannot mature PROPERLY... instead they mature into something weird. Therefore you get a lot of dysfunctional cells. More symptoms arise as the number of dysfunctional cells increases compared to functional. If there is a mutation in these cells which stops them from maturing at all, then they cannot be released from the bone marrow, and it is now called acute myeloid leukaemia. (You would see a mixture of weird and normal cells in the peripheral circulation) The difference between AML and myelodysplasia is that in AML the cells cannot mature at all (so you get lots of blasts) and in myelodysplasia they mature into something weird. Myeloproliferative diseases occur when the normal cell type is produced, but just too much of it. So the maturation is normal, but the rate of proliferation is too high. There are 4 types.... 2 of which are chronic myeloid leukaemia and polycythaemia vera. (you would see immature cells in the peripheral circulation because rate of production is so high) https://www.youtube.com/watch?v=hcuTspQc99s This is a fantastic vid.

What types of phagocyte would respond to the following types of lymphoma: 1. Responds to all types of lymphoma 2. Hodkin's/Non Hodgkin's

1. neutrophil 2. eosinophil (particularly hodgkins, and T-cell NHL). NB.... IL5 stimulates the production of eosinophils (can use antibody against this in treatment of these cancers)

Causes of immature lymphocytosis

ALL

Haem 6 Flashcards

(41 cards)