Myeloma and other plasma cell disorders* Flashcards
where are b cells derived form
pluripotent haemotopoetic stem cells
what are the b cells part of
what are its roles
the adaptive immune system
antibody production
acting as antigen presenting cells
what are immunoglobulins
antibodies produced by b cells and plasma cells
proteins made up of 2 heavy and 2 light chains
each antibody recognises a specific antigen
B cell development
starts in bone marrow
under control of microenvironment
Ig variable element generated from V-D-J region recombination in development
self reactive cells removed
immature b cells with immunoglobulin (Ig) on their surface exit bone marrow ready to meet their target
B cells in the periphery travel to where
identify what
may return
travel to the follicle germinal centre of the LN
identify the antigen and improve the fit by somatic mutation or be deleted
may return to the marrow as plasma cell or circulate as memory cell
plasma cell is what
what dos it do
what does it look like
a factory cell
pumps out antibody
clock face nucleus on H&E
open chromatin - synthesising mRNA
plentiful blue cytoplasm - laden with protein
pale perinuclear area - golgi apparatus
polyclonal increase in immunoglobulins
produced by many different plasma cell clones
suggests theres something wrong
reactive to infection, AI, malig, liver dx
monoclonal rise in immunoglobulins
all derived from a clonal expression of a single B cells
identical antibod structure and specificity
monoclonal immunoglobulin = paraprotein
marker of underlying clonal B cell disorder
how are immunoglobulins detected
what can this detect
serum electrophoresis
abnormal protein bands
which protein precipitate is found on warming the urine and redissolves when heated
BJ proteins
what were BJP identified as and how are they detected
immunoglobulin light chains
detected by urine electrophoresis
how much is the free light chain production by normal plasma cells per day
where does the excess leak into and as what
0.5g/day
into urine as BJP
what are some causes of paraproteinaemia
Walkdenstroms macroglobinulinaemia Chronic lymphocytic leukaemia Solitary of extra medullary plasmocytoma Asymp myeloma Lymphoma Amyloidosis Myeloma MGUS
what is AL amyliodosis
rare disorder small plasma cell clone
mutation in the light chain leading to later structure
precipitates in tissues as an insoluble beta pleated sheet
often presents with late organ damage
how does ALA cause organ damage
progression
systems involved
prognosis
accumulation in tissues
slowly progressive
multisystem dx
poor prognosis esp if cardiac amyloid
organ damage in AL amyloid
kidney - nephrotic syndrome heart - cardiomyopathy liver - organomegaly deranged LFTs neuropathy - autonomic, peripheral GI tract - malabsorption
diagnosis and staging of AL amyloid
organ biopsy - congo red stain
evidence of deposition in other organs - SAP scan, echo, heavy proteinuria
staining in AL amyloid
congo red staining
apple green birefringence under polarised light
Waldenstroms macroglobinunilaemia (IgM paraprotein) is what
lymphoplasmacytoid neoplasm:
clonal disorder of cells intermediate between a lymphocyte and a plasma cells
characterise IgM paraprotein
what are the tumour effects and the paraprotein effects of WM
tumour
lymphadenopathy
splenomegaly
marrow failure
paraprotein
hyperviscosity
neuropathy
what type of antibody is IgM
pentameric
WM clinical features
hyper viscosity syndrome:
fatigue, visual disturbance, confusion, coma, bleeding, cardiac failure
B symptoms- night sweats, weight loss
treatment of WM
chemo
plasmapheresis
what is plasmapheresis
removes paraprotein from the circulation
removes patients plasma rich in IgM paraprotein
replace with donor plasma
