Myeloma Flashcards
What is multiple myelooma?
A disease of plasma cells characterised by uncontrolled replication of a single plasma cell clone, leading to overproduction of one type of immunoglobulin.
A type of bone marrow cancer.
What is a plasma cell?
An antibody-producing B lymphocyte
Note - antibodies are also called immunoglobulins
Pathophysiological of multiple myeloma?
1) Normally a large variety of plasma cells produce various forms of immunoglobulin, however, in myeloma one particular plasma cell clone begins to replicate in an uncontrolled manner.
2) This results in one specific type of immunoglobulin being massively overproduced by the large group of identical plasma cell clones.
3) These plasma cell clones accumulate in the bone marrow, causing reduction in normal blood cell production –> anaemia, leukopenia & thrombocytopniea
How can this spike in a specific form of immunoglobulins be seen on serum and urine electrophoresis?
As a monoclonal band
In addition to crowding out the bone marrow and interfering with normal blood cell production, what can abnormal plasma cells cause?
1) Produce paraprotein –> cause damage to the kidneys by forming protein casts in the renal tubules
2) Secrete factors which activate osteoclasts to break down bone –> widespread lytic lesions, bone pain and hypercalcaemia.
What is a paraprotein (or M protein)?
Abnormal immunoglobulin light chains i.e. an abnormal antibody or part of an antibody
Myeloma vs multiple myeloma?
Multiple myeloma is where the myeloma affects multiple bone marrow areas in the body.
What is monoclonal gammopathy of undetermined significance (MGUS)?
This involves the production of a specific paraprotein without other features of myeloma or cancer.
MGUS is often an incidental finding in an otherwise healthy person.
It has a small risk of progression to myeloma (about 1% per year).
What is smouldering myeloma?
Involves abnormal plasma cells and paraproteins but no organ damage or symptoms.
It has a greater risk of progression to myeloma (about 10% per year).
What are the 5 types of antibodies?
A, G, M, D and E.
Structure of an immunoglobulin?
They are complex molecules made up of heavy chains and light chains arranged in a Y shape.
What does the Bence Jones protein refer to?
Free light chains in the urine
How is myeloma classified?
based on which type of immunoglobulin is produced
What mnemonic can be used to remember the four key features of myeloma?
C - hyperCalcaemia
R - renal failure
A - anaemia
B - bone lesions and bone pain
What is the most common symptom of myeloma?
Bone pain (common areas include the spine and ribs).
Pain typically worsens with activity.
What should persistent pain in a particular area in myeloma raise suspicion of?
A pathological fracture
Cause of bone pain in myeloma?
Due to increased osteoclast activity within the bones creating lytic lesions (and suppressed osteoblast activity).
How are lytic lesions best visualised?
Plain XR
Appearance of lytic lesions on XR?
Punched-out areas (the skull can appear to have a “pepper pot” appearance)
Cause of hypercalcaemia in myeloma?
Due to the resorption of bone
Cause of anaemia & thrombocytopenia in myeloma?
Production of RBCs and platelets is inhibited by plasma cells invading the bone marrow.
Symptoms of anaemia?
Include SOB & fatigue
What type of anaemia is typically seen in myeloma?
Typically normocytic and normochromic
What is often required to maintain an adequate haemoglobin level in myeloma?
repeated transfusions
Symptoms of thrombocytopenia in myeloma?
Often asymptomatic
If platelets reach critically low levels (e.g. <10), symptoms such as petechiae, bruising and bleeding develop
Patients with myeloma often develop renal impairment.
What are some various causes of this?
1) Paraproteins deposited in the kidneys
2) Hypercalcaemia affecting kidney function
3) Dehydration
4) Glomerulonephritis (inflammation around the glomerulus and nephron)
5) Medications used to treat the condition
Symptoms of hypercalcaemia?
constipation, nausea, anorexia and confusion etc
Why are those with myeloma at increased risk of infection?
Patients have abnormally high levels of immunoglobulin, due to the diseased plasma cells. However despite this, the immunoglobulin is mutated, faulty and ineffective.
Production of normal immunoglobulin is also impaired and as a result, patients are significantly immunocompromised.
What neurological symptoms may be seen in myeloma?
1) Confusion, weakness and fatigue – hypercalcaemia
2) Headaches and visual disturbances – hyperviscosity (present in some paraproteinaemia)
3) Peripheral neuropathy – amyloid deposition
4) Limb weakness and loss of bowel/bladder control – spinal cord compression
How is viscosity of the blood affected in myeloma?
Plasma viscosity increases when more proteins are in the blood, such as the paraproteins found in myeloma.
Complications of hyperviscosity of blood?
Hyperviscosity syndrome is considered an emergency. It can cause many issues:
1) Bleeding (e.g., nosebleeds and bleeding gums)
2) Visual symptoms and eye changes (e.g., retinal haemorrhages)
3) Neurological complications (e.g., stroke)
4) Heart failure
Investigations in myeloma?
1) FBC –> anaemia, leukopenia & thrombocytopenia
2) Calcium –> raised
3) ESR –> raised
4) Plasma viscosity –> increased
5) U&Es –> renal impairment
6) Serum protein electrophoresis –> detect paraproteinaemia
7) Serum-free light-chain assay –> detect abnormally abundant light chains
8) Urine protein electrophoresis –> to detect the Bence-Jones protein
What is required to confirm the diagnosis of myeloma?
Bone marrow biopsy
