Myeloma And Plasma Cell Dyscrasias Flashcards
What are B cells derived from?
Pluripotent stem cells
What are immunoglobulins?
Antibodies produced by B cells and plasma cells
What are immunoglobulins made up of?
2 heavy and 2 light chains
They are a protein
What is the Ig region of immunoglobulin generated from?
V-D-J region recombination
What do B cells in the periphery do?
Travel to follicle germinal centre of lymph node
Identify antigen
May return to marrow as plasma cell or circulate as memory cell
What is a plasma cell?
A factory cell that pumps out an antibody
How many clones involved in polyclonal production of immunoglobulins?
Lots of different plasma cell clones
Polyclonal increase in immunoglobulins is a reaction to what?
Infection
Autoimmune
Malignancy
Liver disease
How many clones involved in monoclonal production of immunoglobulins?
One single B cell
What is a monoclonal immunoglobulin called?
Para protein
How do you detect immunoglobulins?
Serum electrophoresis
Serum immunofixation
How does free light chain production happen?
When Ig are synthesised in plasma cells , more light chains than heavy chains made. Free light chains are secreted into plasma with Ig.
Causes of paraproteinaemia ?
MGUS Myeloma Amyloidosis Lymphoma Asymptomatic myeloma Solitary/ extramedullary plasmacytoma Chronic lymphocytic leukaemia Waldenström's macroglobulinaemia
What is myeloma?
A plasma cell malignancy
Affects of myeloma?
Bone lesions Increased calcium Bone pain Marrow failure Renal failure Immune suppression Hyperviscosity Amyloid
What is the most common myeloid?
IgG
Features of hypercalcaemia?
Stones Bones Abdo groans Psych moans Renal impairment Dehydration Thirst
Significance of renal impairment in myeloma?
Tubular cell damage by light chains cast nephropathy Sepsis Hypercalcaemia and dehydration Drugs, NSAIDs Amyloid
How do free light chains cause renal damage?
Normally reabsorbed by proximal tubules
If proximal tubules overwhelmed the light chains can pass into loop of Henle
In ascending limb, tamm-horsfall protein produces and can combine with free light chains
Produces insoluble casts -> block nephron -> renal failure
Treatment of myeloma?
Corticosteroids - dexamethasone , prednisolone
Alkylation agents - cyclophosphamide , lenalidomide
High dose chemo or autologous stem cell transplants
How do you monitor response to treatment in myeloma?
Paraprotein level
Myeloma symptom control?
Opiate analgesia - no NSAIDs
Local radiotherapy
Bisphosphonates
Vertebroplasty
What is MGUS ?
Monoclonal gammopathy of uncertain significance
Is AL amyloidosis common or rare?
Rare
What is the problem in AL amyloidosis?
Mutation In the light chain -> altered structure which precipitates in tissues as an insoluble beta pleated sheet -> organ damage
Prognosis in AL amyloidosis ?
Poor
Organs damaged in AL amyloidosis?
Kidney Heart Liver Neuropathy GI tract
Significant feature of organ biopsy in AL amyloidosis?
Congo red stain
What paraprotein in waldenströms macroglobulinaemia?
IgM
Waldenströms macroglobulinaemia is what type of neoplasia?
Lymphoplasmacytoid neoplasm
Clinical features of waldenströms macroglobulinaemia?
Fatigue Visual disturbance Confusion Coma Bleeding Cardiac failure Night sweats Weight loss
Treatment of waldenströms macroglobulinaemia?
Chemo
Plasmapheresis
