Pathology Flashcards
What are CD markers?
CD = Cluster of differentiation, they are surface proteins which can be used to differentiate erythrocytes
5 tests relevant to multiple myeloma:
- Skeletal survey
- Serum electrophoresis
- Serum calcium
- Serum free light chain assay
- 24 hour urine electrophoresis
Tests involving electrophoresis are looking for what?
Abnormal proteins
Plasma cells are …. and they produce …
- Terminally differentiated B-cells
- Antibodies
Myeloma plasma cells make …. the clinical relevance of this is ….
Monoclonal proteins which serve no function
They can be detected, so aid diagnosis of bone tumours (myelomas)
In immunoglobulin structure the base is …. while the top of the y is …
- Constant
- Variable
In immunoglobulin structure the heavy chain is…
The inner Y shape, continuous from the base to tip (long)
What are the two types of light chain in immunoglobulins?
- K (kappa)
- L (lambda)
Serum free light chain assays look at what part of the immunoglobulin?
The light chain, specifically the ratio of Lambda to Kappa chains
What does the CRAB acronym for multiple myeloma symptoms stand for?
C- High calcium level
R- Renal damage
A- Anaemia
B- Bone destruction
What is the precursor to multiple myeloma?
MGUS»_space;> small amounts of the monoclonal proteins produced by the rubbish plasma cells can be found, but no symptoms
What is smouldering myeloma?
Where lots of monoclonal proteins are being produced by rubbish plasma cells, but there is no organ damage yet
How many cases of MGUS will progress to multiple myeloma per year?
1%
Risk factors for multiple myeloma are:
- Age (increasing)
- Male
- Race (more likely among individuals of African descent)
- Obesity
- Radiation exposure
Of the CRAB symptoms which are the most commonly presenting ones?
- Bone lesions
- Anaemia
Which test detects the majority of multiple myeloma cases?
Serum electrophoresis
What are the sequelae of myeloma bone diseases?
- Low trauma fractures
- Pain
- Reduced quality of life
- Cord compression
Renal disease associated with myeloma is cause by what?
light chain cast nephropathy
> > free immunoglobulin light chains form plugs in the renal tubules
(note= assume renal disease if light chains > 500mg/L)
Factors in addition to light chain cast nephropathy which may contribute to renal disease in multiple myeloma:
- Dehydration
- Hypercalcemia
- Amylodosis
List the steps of amylodiosis in multiple myeloma:
> Cloned dysfunctional plasma cell overproduces unstable immunoglobulin light chains
>Light chains misfold, exposing hidden epitopes which allow interbinding of rubbish light chains
»Can simply deposit in this form causing heart damage
»Can form amyloid fibrils in ordered B-pleated structure which deposit in organs
What organ damage is associated with amyloidosis caused by multiple myeloma?
- Renal
- Periorbital perpura
- Macroglossia
- Nail dystrophy
- Soft tissue damage
- Heart problems
Why are autologous stem cell transplants used in the treatment of myelomas?
Because chemo blitzs the stem cell populations»_space; stops death due to that
What is the process of autologous stem cell transplants?
> remove stem cells from patient using aphresis machine
> freeze them
> replace in patient after chemo
What factors decide if a patient is eligible for
- Younger than 70
- No major comorbidities
List the four drugs classically used in treatment of multiple myeloma and the period of treatment they are associated with:
- Bisphosphonates»_space; all periods of treatment
- Bortezomib»_space; induction (approx 4 months)
- High dose melphalan
- Thalidomide»_space; maintainence (approx 1 year)
Flow cytometry can be used to …
Differentiate clonal from reactive and subtype lymphoproliferative disorders
What are causes of clonal lymphocytosis?
- CD5 lymphoproliferative disorders (including monoclonal B-cell lymphocytosis)
- mantle cell lymphoma
- marginal zone lymphoma
- B-prolymphocytic leukemia
Causes of reactive lymphocytosis:
- Smoking
- Infections (viral, pertussis)
- Psychological stress
- Medications (lithium, natalizumab)
Risk factors for chronic lymphocytic leukemia:
- Genetic
- Living or working on farm or hairdressing
- History of sun exposure
- Age (median diagnosis @ 72)
In terms of pathology chronic lymphocytic leukemia involves:
accumulation of small, mature lymphocytes in the blood, lymp nodes and bone marrow
Whats the pathological difference between small lymphocytis lymphoma and chronic lymphocytic leukemia?
Small lymphocytosis lymphoma»_space; mainly involves the lymph nodes
Chronic lymphocytosis lymphoma involves blood and bone
Is it necessary to bone marrow biopsy to diagnose chronic lymphocytosis lymphoma?
Nope, bloods is enough
Needs to have:
>Large B-cell population in peripheral blood
What is the diagnostic criteria for small lymphocytosis lymphoma?
- small B-cell pop in peripheral blood
- Lymphadenopathy or splenomegaly
CONFIRM with lymph node biopsy if possible
How can genetic lesions in chronic lymphocytosis lymphoma be assessed?
Flourescence in situ hybridization (FISH)
IGHV mutations are…
Immunoglobulin heavy chain variable region mutations
> > Their presence can be used to predict prognosis of chronic lymphocytosis lymphoma
Presenting symptoms of chronic lymphocytosis lymphoma are:
TYPICALLY ASYMPTOMATIC AT PRESENTATION
>fatigue >infections >fevers >weight loss >sweats >painless lymphadenopathy
Chronic lymphocytosis lymphoma sequelae are (3 big groups):
-Impaired immunity (both types)
»increased risk of infections
»increased risk of second malignancies
-Autoimmune cytopenias >>Haemolytic anaemia >>thrombocytopenia >>red cell aplasia >>neutopenia
-Transformation to high grade lymphoma
What are the most common second malignancies associated with chronic lymphocytosis lymphomas:
Skin cancers
What percentage of patients with chronic lymphocytosis lymphoma never require treatment?
25%
What indicates a patient should be treated for chronic lymphocytosis lymphoma?
- Disease related symptoms
- Progressive marrow failure
- Massive/progressive lymphadenopathy
- Massive/progressive splenomegaly
- Lots of rapidly diving lymphocytes
What drugs are appropriate to treat chronic lymphocytosis lymphoma with is TP53 mutation or del(17)p is present?
- Ibrutinib
- Idelasib
- Venetoclax
What causes abnormal bleeding?
- Abnormalities of vasculature
- Defects of primary haemostasis (platelet disorders)
- Defects of secondary haemostasis (procoagulant protein deficiency)
- Accelerated breakdown of a clot (hyperfibrionlysis)
What is anaemia?
Haemoglobin level below the lower limit for their demographic
NOTE: Anaemia is not a diagnosis, just a feature of underlying pathology
What are the symptoms of anaemia?
-Pallor to the skin
- Weakness
- Fatigue
- Lethargy
- Decreased effort tolerance
- Dizziness
- Headaches
- Tachycardia
- Increased pilse pressure
- Cardiac flow murmurs
What causes the following symptoms of anaemia?:
- Weakness
- Fatigue
- Lethargy
- Decreased effort tolerance
- Dizziness
- Headaches
Impaired oxygen delivery to tissue
What causes the following symptoms associated with anaemia?:
- Tachycardia
- Increased pulse pressure
- Cardiac flow murmurs
Cardiac compensation
What are some symptoms associated with anaemia among older patients?
- Cardiac failure
- Angina
- Claudication (cramping the leg due to inadequate blood flow
- confusion
What determines the severity of an episode of anaemia?
- Age of patient
- How rapid onset was
- Hb level
- Degree of physiological compensatio
List 5 ways red cell production can be negatively impacted:
1) Abnormal stem cells
2) Decreased erythropoietin
3) Defective DNA synthesis
4) Defective haemoglobin synthesis
5) Displacement of haemopoietic progenitors
Aplastic anaemia involves abnormal….
stem cells
Failure of which organ results in decreased erythropoietin?
Renal failure (because EPO i
