Myeloma and Other Plasma Cell Dyscrasias Flashcards
Describe B cells
Derived in bone marrow from pluripotent haemopoietic stem cells
Part of the adaptive immune system
What are the roles of B cells?
Antibody production
Antigen presenting cells
What are immunoglobulins?
Antibodies produced by B cells and plasma cells
Proteins made up of 2 heavy and 2 light chains
What do antibodies recognise?
A specific antigen
What do B cells do regarding the periphery?
travel to the follicle germinal centre of the lymph node
Identify antigen and improve the fit by somatic mutation or be deleted
May return to the marrow as plasma cell or circulate as memory cell
Describe a plasma cell
A factory cell Pumps out antibody Open chromatin Plentiful blue cytoplasm (laden with protein) Pale perinuclear area (golgi apparatus)
What is paraprotein?
Monoclonal immunoglobulin
What does electrophoresis detect?
Abnormal protein bands
What 2 light chains are present on antibodies?
Kappa
Lambda
What is the free light chain production by plasma cells?
0.5g/day
What are causes of paraproteinaemia?
Myeloma Amyloidosis Lymphoma Asymptomatic myeloma Loads more
What is a myeloma?
A plasma cell malignancy
What are the direct tumour effects of myeloma?
Bone lesions
Increased calcium
Bone pain
Replace normal bone marrow = marrow failure
What other type of effects can occur from myeloma and what are they?
Paraprotein effects
- renal failure
- Immune suppression
- Hyperviscosity
- Amyloid
How is myeloma classified?
By the type of antibody produced
What are features of hypercalcaemia?
Stones Bones Abdo groans Psychiatric moans Thirst Dehydration Renal impairement
What effects can myeloma have on the kidney?
Tubular damage by light chains Light chain deposition - cast nephropathy Sepsis Hypercalcaemia and dehydration Amyloid Hyperuricaemia Drugs (NSAIDs)
How can you stop light chain production to help with cast nephropathy?
Steroids/chemo
How can you treat myeloma?
Corticosteroids Alkylating agents (cyclophosphamide) Novel agents (thalidomide)
How do you measure the response to treatment for myeloma?
Paraprotein level
How do you control the symptoms of myeloma?
Analgesia (not NSAIDs)
Local radiotherapy
Bisphosphonates
Vertebroplasty (inject cement into fractured bone to stabilise)
What is MGUS?
Monoclonal Gammopathy of Uncertain Significance
Describe MGUS?
Paraprotein <30g/l
Bone marrow plasma cells <10%
No evidence of myeloma or end organ damage
What is AL Amyloidosis?
Rare
Small plasma cell clone
Mutation in the light chain > altered structure
Precipitates in tissues as an insoluble beta pleated sheet
Describe AL Amyloidosis
Accumulation in tissue causes organ damage
Slowly progressive
Multisystem
Different protein to SAA amyloidosis and familial amyloidosis
Poor prognosis espeically if cardiac amyloid
What organ damage can be caused by AL amyloid?
Kidney - Nephrotic syndrome Heart - Cardiomyopathy Liver - Organomegaly deranged LFT's Neuropathy - Autonomic and peripheral GI - Malabsorption
How do you diagnose AL amyloidosis?
Organ biopsy for AL amyloid deposition
Congo red stain
Rectal or fat biopsy
How do you test for deposition in other organs?
SAP can
Echocardiogram
Heavy proteinuria
How does AL amyloid look under polarised light?
Apple-green birefringence
What is Waldenstrom’s Macroglobinaemia?
IgM paraprotein
Lymphoplasmocytoid neoplasm
Clonal disorder of cells intermediate between a lymphocyte and a plasma cell
Characteristic IgM paraprotein
What are the effects of Waldenstrom’s Macroglobinaemia?
Tumour - Lymohadenopathy - Splenomegaly - Marrow failure Paraprotein - Hyperviscosity - Neuropathy
Describe the IgM antibody?
Pentameric
What are clinical features of Waldenstrom’s Macroglobinaemia?
Hyperviscosity syndrome - Fatigue - Bleeding - Cardiac failure Night sweats and weight loss
How do you treat Waldenstrom’s Macroglobinaemia?
Chemo Plasmapheresis (removes protein from the circulation)
