Haematology Flashcards
What is myeloma?
Cancer of differentiated B lymphocytes (plasma cells)
Describe the pathophysiology of myeloma
Accumulation of malignant plasma cells in bone –> progressive bone marrow failure
Production of one excess immunoglobulin (monoclonal paraprotein)
What monoclonal paraprotein is usually produced in myeloma?
IgG = 55% IgA = 20%
What is mono-clonality?
Abnormal proliferation of a single clone of plasma cell leading to immunoglobulin secretion and causing organ dysfunction especially to the kidney
Give 3 symptoms of myeloma
- Tiredness
- Bone/back pain
- Infections
Give 4 signs of myeloma
CRAB
- Calcium is elevated
- Renal failure
- Anaemia
- Bone lesions
Why is calcium elevated in myeloma?
Increased bone resorption and decreased bone formation so more calcium in the blood
Why might someone with myeloma have anaemia?
BM infiltrated with plasma cells = anaemia, neutropenia (infections) and thrombocytopenia (bleeding)
Why might someone with myeloma have renal failure?
Due to light chain deposition
What investigations might you do in someone who you suspect has myeloma?
- Bloods and blood film
- Blood marrow aspirate and trephine biopsy
- Electrophoresis
- X-ray
- Urinalysis
What would you expect to see on the blood film taken from someone with myeloma?
Rouleaux formation (aggregation of RBCs)
What are you looking for on a bone marrow biopsy taken from someone with myeloma?
Increase plasma cells
What are you looking for on electrophoresis in a patient with myeloma?
Monoclonal protein band
What would you expect to see on the x-ray taken from someone with myeloma?
Lytic ‘punched out’ lesions –> pepper pot skull, vertebral collapse
Fractures
Osteoporosis
What might the urine of someone with myeloma contain?
Bence-jones protein - immunoglobulin light chains with kappa or lamda lineage
What does a diagnosis of myeloma require?
- Monoclonal protein band in serum or urine
- Increased plasma cells on bone marrow biopsy
- Hypercalcaemia/renal failure/anaemia
- Bone lesion on skeletal survey
Describe the treatment for symptomatic myeloma
Bone pain = analgesia Bisphosphonates (zolendronate) Blood transfusion - for anaemia Fluids and dialysis - renal failure Chemotherapy Stem cell transplant
How is myeloma bone disease usually assessed?
X-ray
Suggest 3 ways in which multiple myeloma can lead to AKI
- Deposition of light chain
- Hypercalcaemia
- Hyperuricaemia
What kind of anaemia is seen in patients with multiple myeloma?
Normochromic normocytic
What chemotherapy regime is used in patients with myeloma?
VAD (fitter people) or CTD (less fit people)
What is leukaemia?
A malignant proliferation of haemopoietic stem cells (immature blood cells)
Name 4 sub types of leukaemia
- AML - Acute Myeloid Leukaemia
- CML - Chronic Myeloid Leukaemia
- ALL - Acute Lymphoblastic Leukaemia
- CLL - Chronic Lymphoblastic Leukaemia
What is acute myeloid leukaemia (AML)?
Neoplastic proliferation of blast cells (immature blood cells)
Acute malignant transformation of myeloid progenitor cells
What can increase the risk of developing AML?
- Preceding haematological disorders
- Prior chemotherapy
- Exposure to ionising radiation
- Down’s syndrome
Give 5 symptoms of leukaemia
- Anaemia
- Infection
- Bleeding
- Hepatomegaly
- Splenomegaly
Why are anaemia, infection and bleeding symptoms of leukaemia?
Because of bone marrow failure
Why are hepatomegaly and splenomegaly symptoms of leukaemia?
Because of tissue infiltration
What investigations do you do on someone who you suspect has leukaemia?
- Blood film
- Bone marrow biopsy
- Lymph node biopsy
- Immunophyenotyping
- Cytogenetics
What would you expect to see on a blood film and bone marrow biopsy in someone you suspect to have AML?
Blood film = anaemia and thrombocytopenia
BM biopsy = leukaemic blast cells
Describe the treatment for AML
- Supportive therapy (blood transfusions, infections prophylaxis etc)
- Chemotherapy - curative vs palliative
- Bone marrow transplant
What is chronic myeloid leukaemia (CML)?
Uncontrolled clonal proliferation of myeloid cells (basophils, eosinophils and neutrophils)
What chromosome is present in >80% of people with CML?
Philadelphia chromosome
Give 4 symptoms of CML
Insidious onset
- Symptomatic anaemia
- Abdominal pain - splenomegaly
- Weight loss
- Tiredness
- Gout
- Bleeding
What would the FBC from someone with CML look like?
High WCC
Anaemia - normochromic and normocytic
What is the treatment for CML?
Imatinib = tyrosine kinase inhibitor
Stem cell transplant
Why does the Philadelphia chromosome cause CML?
Froms fusion gene BCR/ABL on chromosome 22 –> tyrosine kinase activity –> stimulates cell division
What is acute lymphoblastic leukaemia (ALL)?
Uncontrolled proliferation of immature lymphoblast cells (lymphoid progenitor cells)
Acute malignant transformation of lymphoid progenitor cells
Give 4 signs of ALL
- BM failure
- Heaptosplenomelgay
- Lymphadenopathy
- Headache and CN palsies
- Mediastinal masses with SVC obstruction
Due to organ infiltration
What is the treatment for ALL?
Chemotherapy
Supportive therapy - Blood and platelet transfusion, Allopurinal (prevents tumour lysis syndrome)
Bone marrow transplant
What is Chronic lymphoblastic leukaemia (CLL)?
Proliferation of mature B lymphocytes leads to accumulation of mature B cells that have escaped apoptosis
Chronic malignant transformation of mature lymphoid cells
What may be seen on the blood film of someone with CLL?
Smudge cells on histology
What is the treatment for CLL?
- Do nothing
- Chemotherapy
- Monoclonal antibodies
- Bone marrow transplant
Is ALL more common in adults or children?
Mainly a childhood disease
Give 4 symptoms of ALL
- Bone pain
- Recurrent infections (neutropenia)
- Pale and tired (anaemia)
- Bruising (low platelets)
Give 3 environmental causes of leukaemia
- Radiation exposure
- Chemicals (benzene compounds)
- Drugs
What is lymphoma?
Malignant proliferation of lymphocytes, normally in the lymph nodes
Although predominantly in the lymph nodes, what other organs can lymphoma effect?
- Blood
- Bone marrow
- Liver
- Spleen
Give 4 risk factors for lymphoma
- Primary immunodeficiency
- Secondary immunodeficiency - HIV, transplant recipients
- Infections - EBV, H. pylori, HTLV-1
- Autoimmune disorders - SLE, RA
Describe the pathophysiology of lymphoma
Impaired immunosurveillance and infected B cells escape regulation and proliferate
Give 4 symptoms of lymphoma
- Enlarged lymph nodes in arm/neck
- Symptoms of compression syndromes
3, General systemic ‘B’ symtoms - weight loss, night sweats, malaise - Hepatosplenomeglay
What investigations might you do in someone who you suspect has lymphoma?
- Blood fim
- Bone marrow biopsy
- Lymph node biopsy
- Immunophenotyping
- Cytogenetics (karyotyping/FISH)
What staging investigations might you do in someone with lymphoma?
- Blood tests
- CT scan chest, abdomen, pelvis
- Bone marrow biopsy
- PET scan
What are the 2 sub-types of lymphoma
- Hodgkins lymphoma
2. Non-hodgkins lymphoma
What are symptoms of Hodgkins lymphoma?
- Painless lymphadenopathy
2. Presence of ‘B’ symptoms - fever, weight loss, night sweats, lethargy
What is needed for the diagnosis of Hodgkins lymphoma?
Presence of Reed-Sternberg cells (in lymph node biopsy)
What blood results may you seen in someone with Hodgkins lymphoma?
High ESR
Low Hb
High serum lactase dehydrogenase
Describe the staging go Hodgkins lymphoma
Stage 1 = confined to a single lymph node region
Stage 2 = Involvement of two or more nodal areas on the same side of the diaphragm
Stage 3 = Involvement of nodes on both sides of the diaphragm.
Stage 4 = Spread beyond the lymph nodes e.g. liver.
Each stage is either ‘A’ - absence of ‘B’ symptoms or ‘B’ - presence of ‘B’ symptoms
What is treatment for stage 1 - 2A Hodgkins lymphoma?
Short course chemotherapy followed by radiotherapy
What is the treatment for stage 2B - 4 Hodgkins lymphoma?
Cyclic chemotherapy and radiotherapy
What chemotherapy regime is used for the treatment of Hodgkins lymphoma?
ABVD regime: Adriamycin Bleomycin Vinblastine Dacarbazine
What treatment is used for a relapse of Hodgkins lymphoma?
Stem cell transplant
What are the possible complications of treatment for Hodgkins lymphoma?
- Secondary malignancies
- IHD
- Infertility
- Nausea
- Alopecia
What is non-hodgkins lymphoma?
Any lymphoma not involving Reed-Sternberg cells
Describe low-grade non-hodgkins lymphoma
E.g. Follicular lymphoma
Slow growing
Often advanced at presentation
Often incurable (mens survival 10 years)
Describe high grade non-hodgkins lymphoma
E.g. Diffuse Large B cell Lymphoma
Agressive
Nodal presentation
Often curable
Give an example of a very high grade Non-Hodgkin’s lymphoma
Burkitt’s lymphoma
Give 4 features of non-hodgkins lymphoma
- Lymphadenopathy - painless
- Extranodal involvement - skins, CNS
- Systemic symptoms - fever, weight loss, night sweats
- Pancytopenia - anaemia, thrombocytopenia and leukopenia due to BM involvement
What is the treatment for low grade non-hodgkins lymphoma?
If symptomless - do nothing
Radiotherapy, combination chemotherapy and monoclonal antibodies may be used if symptomatic
What is the treatment for high grade non-hodgkins lymphoma?
Early = short course chemotherapy and radiotherapy Advanced = combination chemotherapy and monoclonal antibody (Rituximab)
What is anaemia?
A reduced RBC mass +/- reduced Hb concentration
What is the functions of Hb?
It carries and delivers oxygen to tissues
What are the normal Hb concentrations for:
a) Males
b) Females
a) Males = 131-166 g/L
b) Females = 110-147 g/L
What organs are responsible for the removal of RBCs?
- Spleen
- Liver
- Bone marrow
- Blood loss
What are the normal MCV values for:
a) Males
b) Females
a) Males = 81.8-96.3 fl
b) Females = 80.0-98.1 fl
Give 3 causes of microcytic anaemia
- Iron deficiency
- Chronic disease
- Thalassaemia