Lab investigation of WBC Flashcards
What are the main functions of neutrophils?
Chemotaxis, phagocytosis and killing of bacteria
What are the main functions of eosinphils?
- Same as neutrophils, but also involved in the late phase of immediate-type hypersensitivity reactions
What are the main functions of basophils?
Have high affinity IgE receptors, involved in acute hypersensitivity reactions (histamine release)
What are the main functions of monocytes/macrophages?
Chemotaxis, phagocytosis, killing MOs, APC, release of IL-6, TNF, G-CSF etc
What are the main functions of lymphocytes?
Involved in immune responses, production of Ab and haematopoeitic GFs
What is the stem cell hierarchy?
- HSC
- Give rise common lymphoid progenitor -> lymphoblast -> B-cell or T-cell
- Also give rise to common myeloid progenitor -> RBCs or platelets, OR myeloblast -> WBCs
- Need cytokines such as G-CSF, M-CSF and GM-CSF to differentiate from myeloblasts
What happens when bone marrow neutrophils mature?
- Increasingly differentiated and lose the capacity for self-renewal as they mature
- A single stem cell give rise after multiple divisions, to >10^6 mature cells
What are the 5 actions GFs may have on bone marrow cells?
- Proliferation of early cells
- Differentiation of early cells
- Maturation
- Suppression of apoptosis
- Functional activation
What is the process of neurophil margination?
- Neutrophils in peripheral blood exist either in the circulating or marginated pool
- Marginated neutrophils roll along the blood vessel wall, where their surface carbohydrates interact with selectins on endothelial cells
- After activation by chemotactic agents, neutrophils change shape and change the affinity of their integrin molecules for endothelial cell intracellular adehesion molecules
- The neutrophils then crawl and undergo diapedesis, by interacting with platelet-endothelial cell adhesion molecules on the endothelial surface, and by liberating hydrolases that permit passage of the neutrophils through the capillary basement membrane
How do neutrophils kill pathogens?
- Bacterium invades a host cell and injures it
- Bacterial products, Abs and complement cause the release of chemotactic factors - activate neutrophil in adjacent blood vessel
- Neutrophil adheres to vessel wall, undergoes chemotaxis and diapedesis into tissue, to follow chemoattractants to their site of generation
- Neutrophil ingests bacterium-antibody-complement complex, forming a phagosome
- Neutrophil degranulates, releasing various enzymes and enhances oxidative metabolism, the products of which are bactericidal
What is the physiology of monocytes?
- Spend 48-72 hrs in circulation, then migrate into the tissues and become immature macrophages -> mature macrophages
- These have phagocytic and scavenging functions
- Macrophages also store and release iron
Whats the physiology of lymphocytes?
- Lymphoid stem cell gives rise to T, B and NK cells
- Lymphocytes recirculate to lymph nodes and other tissues, then return to bloodstream
- Lymphocytes have variable lifespan
Why may cell count increase?
Increased production
- Normal haematopoeisis in response to high altitude, infection, bleeding etc
- Abnormal haematopoeisis producing too many cells - leukaemia, polycythaemia vera, thrombocythaemia
Decreased destruction
- leukaemia, malignant cells
Why might cell number decrease?
Production decreased
- Reduced haematinic agents (iron, vit B12 deficiency)
- Bone marrow damage (chemo, radiotherapy, cancer)
- Abnormal haematopoeisis (leukaemia, myelodysplasia)
Increased destruction
- Abnormal cels (sickle)
- Abnormal environment (immune damage)
How do we investigate a raised WBC?
- History and examination
- FBC
- Differential leukocyte count
- Examine blood film
- Does the abnormality affect WBCs only, or RBCs and platelets too?
- Does it affect 1 cell type, or all cell types? (e.g. neutophils, eosinophils, lymphocytes, monocytes)
- Does it affect mature cells only? or both mature and immature?
What is neutrophilia?
- Increased neutrophils in blood
- >10 /10^9/L
How can neutrophilia develop?
- Demargination
- Early release from bone marrow
- Increased production (infection)
. acute bacterial infections
. acute inflammation - haemorrhage and haemolysis
- drugs - steroids and growth factors
- malignancy - haematological or non-
What is neutropaenia?
- Low levels of neutrophils
- <1 / 10^9/L
How can neutropaenia develop?
- Chemo/radiotherapy
- Bone marrow failure
- drugs (not cytotoxic)
- Infections
- immune neutropaenia
- Afro-Caribbean persons
What is lymphocytosis?
Non-malignant
- infants and young kids
- infections - viral, TB, syphilis, toxoplasmosis
- Post-splenectomy
- Thyrotoxicosis
Malignant
- CLL
- ALL
- Non-hodgkin lymphoma
What are the 5 main malignant blood disorders?
- Leukaemias (acute and chronic)
- Lymphomas
- Paraproteinaemias
- Myeloproliferative neoplasms
- Myelodyplastic syndromes
What are the 4 leukaemias?
ALL, AML, CLL, CML
What are the myeloproliferative neoplasms?
- Polycythaemia vera (PV)
- Essential thrombocythaemia
- Primary myelofibrosis (MF)
What is a leukoerythroblastic anaemia?
Any anaemic condition resulting from space-occupying lesions in the bone marrow; the circulating blood contains immature cells of the granulocytic series and nucleated red blood cells
What can cause leukoerythroblastic anaemia?
Malignant
- cancer, leukaemia, myeloma, lymphoma, myelofibrosis
Non-malignant
- haemolysis, megaloblastosis, TB, osteopetrosis
What is a lymphoma?
A malignant tumour of lymphoid cells affecting lymph nodes and extra-nodal sites
- Hodgkin and non-Hodgkin
- 80% B cells, 20% T cells
What is multiple myeloma?
- A disease involving plasma cell malignancy
- Causes bone pain and fractures, recurrent bacterial infections, renal failure, bone marrow failure, hypercalcaemia, amyloidosis, hyperviscosity
What do we see in the lab from myeloma?
- Monoclonal band
- Bence jones proteinuria
- Free light chains in serum
- Abnormal plasma cells in bone marrow
- Anaemia, neutropaenia, thrombocytopaenia
- rouleaux formation - High ESR
- Osteolytic lesions, osteoporosis, fractures
- Electrophoresis = big peak in gamma globins
