Haematology (White blood cells) Flashcards
What is the normal concentration range of WBC in the blood?
4-10 x 10^9/L
What is the only immature WBC that leaves the bone marrow?
T lymphocytes
Therefore, what does the presense of immature WBCs (other than T cells) in the blood indicate?
Disease
Name 2 diseases resulting from granulocyte defects?
1) Acute myeloid leukemia
- increase in the number of myeloblasts in bone marrow or peripheral blood
2) Actute promyelocytic leukaemia
- Increase number of promyelocytes
- Not associated with increases in more differentiated types
What is a Leukaemoid Reaction?
Defined as a leucocyte count in excess of 50 x 10^9/L with all stages of myeloid maturation (including myeloblasts)
Leukaemoid reaction can be difficult to distinguish from what disease?
Chronic myeloid leukaemia (CML)
What is a main difference between leukaemoid reaction and true leukaemia?
Cells of leukaemoid reaction are polyclonal
True leukemia cells usually monoclonal (derived for a single cell type)
What are some causes of leukaemoid reaction?
- Corticosteroids
- Haemorrhage
- Haemolysis
- Alcohol intoxication
What is neutropenia in response to acute tissue damage/infection?
Neutrophils migrate in large numbers from the bone marrow to the periphery, depleting the marrow reserves
What is neutrophilia?
A neutrophil count in excess of the normal range
- immature neutrophils in peripheral blood, contain granules with high concs of acid mucosubstances capable of fighting infection
What is neutrophilia usually a result of?
Blood borne infectons, known as sepsis
What does Pelger-Huet anomaly result in?
Hyposegmented ( 2 nuclear lobes or fewer) neutrophils with a singular or bilobed nucleus
What is Kostmann Syndrome?
- Congenital severe combined neutropenia commonly diagnosed in first year of life
(0. 2 x 10^9/L)
60% of Kostmann syndrome patients have mutations in what?
Gene encoding neutrophil elastase (ELA2)
30% of Kostmann syndrome patients also have defects in what?
HAX1, the gene encoding HS-1 associated protein X (HAX)
What is the result of HAX mutations?
Plays an important role in apoptosis
- cells deficient in HAX undergo premature apoptosis in the bone marrow
Patients with Kostmann syndrome are at risk of developing what?
- Myelodysplastic syndrome or AML
Describe the process of granule release from neutrophils in patients with sepsis
Approx 300 different protein types selectively distributed between primary, secondary and tertiary granules
Released at different times to induce toxic response and inflammation to foreign objects
What are hypersegmented neutrophils and when can they be seen?
- Average of 5 lobes or more in the nucleus
- Occurs in many infections
- Iron deficiency
- Uraemic patients
What is megaloblastic anaemia? What is the cause and consequence?
Megaloblastic anaemia develops as a result of vitamin B12 deficiency
- DNA replication compromised, cell cycle arrest during S phase
- Results in macropolycytes - enlarged cells with double DNA
What are the 3 main proteins found in neutrophil granules and which are they found in (primary, secondary etc)
1) Myeloperoxidase (MPO)
- haem containing enzyme involved in non-specific pathogen elimination
- Primary granules
2) Lactoferrin
- sequencers iron, prevents bacterial growth
- secondary granules
3) Gelatinase - metalloprotease that digests collagen, allowing movement through basement membrane of blood vessels (diapedesis)
How are eosinophils involved in mediating hypersensitivity?
Counteract the effects of basophils and mast cells by secreting prostaglandins
What is another key role of eosinophils?
Destruction of helminths (e.g worms)
What count is considered eosinophilia? What is it caused by?
- 0.5 x 10^9/L
- allergy or inflammation
- helminth infection
- hodgkin lymphoma
- chronic eosinophilic leukemia
What occurs in prolonged eosinophilia?
Severe tissue damage
Eosinophils in severe allergy have secondary granules that stain orange with eosin due to the presence of what?
Bacteriocidal arginine-rich basic proteins
What count is basophilia?
0.1 x 10^9/L
When does basophilia occur?
- Acute hypersensitivity reactions
- Haematological malignancies e.g CML
- Advancing CML is associated with progressive basophilia
What can occur to macrophages during severe chronic inflammation?
May undergo endomitosis
- replication of the nucleus in the absense of cell division to produce giant cells
What is a raised peripheral blood lymphocyte count called?
lymphocytosis
What can cause lymphocytosis?
Viral infections
Bacterial infections
Haematological maligancies
What is the name for a reduced lymphocyte count?
Lymphopenia
What can cause lymphopenia?
Trauma or infection
Acute or chronic immunosuppression
What is an indicator of NK cell leukaemia?
Large numbers of circulating NK cells
What is the difference between normal NK cells and NK cells in leukemia?
Within an NK cell population, leukemia has more NK cell with large cytoplasms with cytoplasmic granules
What is Infectious mononucleosis? What is it caused by?
- A benign lymphoproliferative disorder
- Caused by infection of B cells with Epstein-Barr virus (EBV)
- Binds to CD21 receptor on B cell membrane
How to B cells respond to EBV infection?
Produce anti-EBV antibodies
What % of adults worldwide are seropositive? (possess antibodies against EBV)
80-90%
What are the symptoms of IM?
Fever Malaise Chills Sore throat Enlarged lymph nodes
Name some characteristics of the full blood count in IM
1) Leukocytosis (12-25 x 10^9/L)
2) Neutropenia and thrombocytopenia may be evident
3) Scalloping of the membrane around neighboring red cells
How is IM diagnosed?
Patients with IM have heterophile antibodies (also called Paul-Bunnell antibodies)
Antibodies detected by standard latex agglutination test
Name a more specific test for EBV infection
Antibodies against:
- viral capsid antigen (VCA)
- nuclear antigen (EBNA)
Where are plasma cells usually restricted too?
The bone marrow and lymphoid organs
What can cause the appearance of plasma cells in the peripheral blood (plasma cell leukemia)?
Acute infections or haematologial malignancies
How can plasma cells in the peripheral blood be identified?
- Eccentric (off centre) shaped nucleus
- deeply basophilic (blue) cytoplasm
What is the structure of a plasma cell nucleus?
- clumped chromatin
- surrounded by a prominent golgi zone known as the perinuclear halo
