The White Cell Flashcards
What cell types are included in a WC differential?
Neutrophils Lymphocytes Eosinophils Monocytes Basophil
What is the function of Neutrophils?
Ingest/kill bacteria, fungi, cellular debris
What is the function of Lymphocytes?
Produce antibodies for cell-mediated immunity
What is the function of Eosinophils?
Role in allergic reactions, defence of parasitic infection
What is the function of Monocytes?
Precursor to tissue macrophages
What is the function of Basophils?
Release histamine in inflammatory reactions
What is Leukocytosis?
Increase in WCC
What are the causes of a neutropenia?
Viral infection Severe sepsis Neutrophil antibodies (SLE) Bone marrow failure Hypersplenism Cytotoxic drugs
What are the causes of a neutrophilia?
Bacterial infection Inflammatory reactions Disseminated malignancy Stress Myeloproliferative conditions Corticosteroid therapies
What is agranulocytosis, and what drug causes it as a s/e?
Complete absence of circulating neutrophils
Carbimazole
What are the causes of a lymphopenia?
Bone marrow failure Corticosteroid therapies SLE Uraemia HIV infection Cytotoxic drugs
What are the causes of a lymphocytosis?
Viral infections
Chronic infections
Myeloproliferative conditions
What are leukaemias?
Malignant proliferations of blood forming cells
- acute/chronic
- myeloid/lymphoid
Describe the difference b/w myeloid/lymphoid cell lineages?
Haemopoietic stem cell –> common myeloid/lymphoid progenitor
- common myeloid –> erythrocytes, mast cells, megakaryocytes (form platelets), myeloblasts
- common lymphoid –> NK cells, T/B lymphocytes
What cell lines do myeloblasts go on to form?
Monocytes
Basophils
Neutrophils
Eosinophils
What are the myeloproliferative conditions?
Myelofibrosis
Myelodysplasia
Polycythaemia vera
PRE-LEUKAEMIC
What is Acute Lymhoblastic Luekaemia (ALL)?
Malignancy of lymphoid cells (T/B cells) leading to uncontrolled proliferation of immature blast cells
-eventual bone marrow failure & tissue infiltration
What is the aetiology of ALL?
Most common childhood malignancy
- 3-7yrs average age of dx
- 80% of childhood leukaemias
- rare in adults
- more common in certain syndromes (e.g. Downs)
What is the prognosis of ALL?
Children (<10yrs) = good, cure rates >80%
What are poor prognostic factors in ALL?
Older age of presentation Male sex B-cell disease Presence of Philadelphia chromosome -9:22 translocation
What is Acute Myeloid Leukaemia (AML)?
Malignancy of blast cells from marrow myeloid elements
What are the risk factors for AML?
Can be de novo OR Myeloproliferative conditions Previous chemo Ionising radiation Genetic syndromes
What is the aetiology of AML?
Median age of presentation at 65 yrs
- can occur at any age
- incidence increases w/ age
What is the prognosis of AML?
Rapidly progressive
20% 3yr survival after chemo
How do acute leukaemias present?
B sx
Bone pain
Sx of marrow failure
Hepatomegaly/splenomegaly
What are B sx?
Fatigue Wt loss Night sweats Fevers Pruritis
What are the sx of marrow failure?
Anaemia (SOB on exertion, weakness)
Leukopenia (recurrent infections)
Thrombocytopenia (bleeding & brusing)
What is important to remember about the leukopenia in acute leukaemias?
Pts have leukocytosis BUT immature cells so present as leukopenia
What investigations are appropriate in suspected acute leukaemia?
FBC Blood film CXR (T-cell ALL, ?mediastinal widening) Bone marrow aspiration PET scanning (?mets) U&Es, LFTs, cardiac function testing
What are the general principles of managing acute leukaemias?
Supportive care
Use of antibiotics
What supportive care should be given in acute leukaemia?
Nurse w/ full barrier nursing Hickman line inserted High-calorie diet Frequent blood/platelet transfusions Allopurinol (prevent tumour lysis syndrome) Frequent bloods/obs
When should antibiotics be given in acute leukaemia?
Temp >38o on 2 occassions >1hr apart
- assume sepsis
- start broad spectrum a/b until afebrile for 72 hrs
- often cephalosporin + gentamycin
What specific management steps are taken in ALL?
High dose chemo to induce remission -consolidation w/ high/med dose blocks over months -2 yrs maintenance therapy Consider marrow transplant -necessary if Philadelphia chromosome
What specific management steps are taken in AML?
Intensive chemo If poor prognosis -allogenic marrow transplant from HLA-matched siblings -allows further high dose chemo If intermediate prognosis -autologous marrow transplants -further, lower dose chemo
What is the aetiology of Chronic Myeloid Leukaemia (CML)?
Rare in childhood
Most common 40-60yrs
Philadelphia Chr present in 95%
-better prognosis
What are the sx of CML?
Insidious B sx, detected by chance (30%) Gout (purine breakdown) Abdo discomfort (splenomegaly)
What are the signs of CML?
Splenomegaly
Hepatomegaly
Anaemia/thrombocytopenia
What investigations are appropriate in suspected CML?
FBC (WCC inc) Blood film (myeloid cells inc) Bone marrow biopsy CT/PET Cytogenic analysis of blood/marrow for Philadelphia Chr
What are the management options for CML?
Imatinib chemo -response rate >90% Stem cell transplantation -only treatment to achieve remission -significant mortality/morbidity
What is the prognosis of CML?
Median survival 6yrs
What are the three stages of CML?
Chronic phase -few sx, lasts for yrs Accelerated phase -inc sx, difficulty controlling counts Blast transformation -features of AML, death
What is the aetiology of Chronic Lymphocytic Leukaemia (CLL)?
Most common leukaemia
2x as common in males
Median age of presentation 7yrs
What is the underlying pathophysiology of CLL?
Accumulation of mature B-cells (escaped apoptosis)
Inc mass of immune-incompetent cells –> Bone marrow failure
What are the sx of CLL?
Asymptomatic, incidental finding on FBC
Anaemic/infection prone
B sx (if severe)
What are the signs of CLL?
Enlarged, non-tender lymph nodes
Hepatosplenomegaly
What investigations are appropriate in suspected CLL?
FBC (inc WCC, AI haemolysis later) Blood film (smudge cells)
What is the rule of 1/3s for CLL?
W/o treatment
- 1/3 will never progress
- 1/3 will eventually progress
- 1/3 will progress from diagnosis
What are the management options for CLL?
Treatment only indicated if symptomatic/markers of poor prognosis
Chemo/radio
What is the prognosis of CLL?
Depends on Rai stage, anywhere from 1yr to 13yrs mean survival
-death usually due to infection/Richter’s syndrome
What is Richter’s syndrome?
Transformation of CLL to aggressive lymphoma
-usually diffuse large B cell lymphoma
What is myeloma?
Malignant clonal proliferation of plasma cells (derived from B lymphocytes)
What is the monoclonal band/paraprotein of myeloma?
Single clone of plasma cells produce single immunoglobulin
-seen on serum/urine electrophoresis as monoclonal band
What is the aetiology of myeloma?
Average age presentation 70yrs
More common in Afro-Carribean populations
What are the core clinical features of myeloma?
CRAB
- calcium (hypercalcaemia)
- renal (impairment)
- anaemia (bone marrow failure)
- bone (osteolytic lesions due to osteoclast activation)
What are the presenting sx of myeloma?
Backache Pathological fractures Hypercalcaemia (bones, stones, moans, groans) Infection Anaemia Bleeding Renal impairment (20% at dx)
What investigations are appropriate in suspected myeloma?
FBC (normochromic, normocytic anaemia, WCC dec) Blood film (rouleaeux) ESR (raised) U&Es (deranged) Ca (raised) Alk Phos (norm) Serum/urine electrophoresis Urine Bence-Jones protein (+ve) Skeletal XR (lytic lesions) Bone marrow biopsy
What are the management options for myeloma?
Supportive therapy
Chemotherapy
Radiotherapy
Bone marrow stem cell transplants if <70
What are the complications of myeloma?
Hypercalcaemia
Spinal cord compression
Hyperviscosity
Acute renal failure
What is the prognosis of myeloma?
Original cell v. resistant, often returns
Med survial 3-4yrs
Death from renal failure/infection
What are lypmhomas?
Malignant proliferations of lymphocytes, usually B-cells
- commonly accumulate in peripheral lymph nodes
- can accumulate in peripheral blood/infiltrate organs
What are the two main types of lymphoma?
Hodgkin’s (15%)
Non-Hodgkin’s (85%)
What is the defining characteristic of Hodgkin’s lymphoma?
Presence of Reed-Sternberg cells
-binucleate ‘mirror cells’ on biopsy
What is the aetiology of Hodgkin’s lymphoma?
Peak incidence at 20-35yrs & 50-70yrs
More common in males (2:1)
What are the risk factors for Hodgkin’s lymphoma?
Affected sibling
EBV
SLE
Obesity
What are the sx of Hodgkin’s lymphoma?
B sx, w/ profuse night sweats (25%)
Lymph node pain induced by alcohol
SVC/bronchial obstruction
Pleural effusion
What are the signs of Hodgkin’s lymphoma?
Enlarged, non-tender, rubbery lymph nodes (cervical)
Lymphaenopathy
Hepato-splenomegaly (50%)
Cachexia/anaemia
What is the prognosis of Hodgkin’s lymphoma?
Slow growing, localised, rarely fatal
Better in lymphocyte predominant disease
What is the aetiology of Non-Hodgkin’s lymphoma?
All lymphomas w/o Reed-Sternburg cells
Peak incidence at 70yrs
What are the two main classifications of Non-Hodgkin’s lympoma?
High grade
Low grade
Describe high grade Non-Hodgkin’s lymphoma
Divide rapidly
Present w/ rapid onset lymphadenopathy
Aggressive
Better prognosis if identified/treated
Describe low grade Non-Hodgkin’s lymphoma
Divide slowly
Present insidiously
Widely disseminated at dx
Often incurable
What are the sx of Non-Hodgkin’s lymphoma?
Nodal disease (lymphadenopathy in 75%) Extranodal disease (25%) -oropharynx, skin, CNS, gut or lung B sx (wt loss if disseminated) Bone marrow failure
What are the appropriate investigations in Non-Hodgkin’s lymphoma?
Bloods - FBC, ESR, LFT, U&Es, LDH, Ca
Lymph node excision biopsy
Image guided biopsy
Staging CT
What are the management options for Non-Hodgkin’s lymphoma?
Chemotherapy
Radiotherapy
Chemo-radiotherapy
What is the prognosis for Non-Hodgkin’s lymphoma?
Survival variable Poor prognostic signs are ->60yrs -disseminated disease -raised LDH
How are Non-Hodgkin’s lymphomas stages?
Ann-Arbor system
What are myeloproliferative disorders?
Disease where clones of haemopoetic stem cells proliferate in the marrow, but retain the ability to differentiate
What are the common myeloproliferative disorders?
Essential thrombocytosis
Myelofibrosis
Polycythaemia rubra vera
What is essential thrombocytosis?
Clonal proliferation of megakaryocytes –> persistently raised platelets
-often asymptomatic
What are the sx of essential thrombocytosis?
Often asymptomatic
Microvascular occlusion
Bleeding sx
Arterial/venous thrombosis
What is Polycythaemia rubra vera (PCV)?
Malignant proliferation of a clone derived from one pluripotent marrow cell
-not requiring EPO to avoid apoptosis
What are the common sx of PCV?
Asymptomatic
Arterial/venous thrombosis (>60yrs)
What are the main complications of PCV?
Serum hyperviscosity (excess RBCs & WCs) Thrombotic complications (excess platelets)
How is PCV diagnosed?
Increased red cell mass
Investigation for JAK 2 mutation
What are the rarer presentations of PCV?
Vague hyperviscosity sx (headache, dizziness, tinnitus, facial plethora, erythromelagia)
Splenomegaly
Gout
How is PCV managed?
Repeated venesection
Low dose aspirin
What is erythrromelagia?
Burning sensation in fingers/toes
What is Primary Myelofibrosis?
Hyperplasia of megakaryocytes
- produces excess platelet derived growth factor
- marrow fibrosis & metaplasia
- 2o haematopoiesis in spleen
What are the sx of Primary Myelofibrosis?
B sx
Abdo discomfort (massive splenomegaly)
Bone marrow failure
What is the main risk of essential thrombocytopenia & PCV?
May progress to myelofibrosis OR AML
-risk relatively rare
What is aplastic anaemia?
Stem cell disorder leading to pancytopenia/hypoplastic marrow
What are the causes of aplastic anaemia?
Autoimmune (drugs, viruses, irradiation as triggers)
Inherited (Fanconi)
What are the sx of aplastic anaemia?
Bone marrow failure
Pancytopenia
How is aplastic anaemia diagnosed?
Bone marrow biopsy
How is aplastic anaemia managed?
Blood product transfusion Immunosuppression in AI Allogenic bone marrow transplant -curative -only in younger pts
