myeloma and other dyscrasia Flashcards
what is the function of B cells
antibody production
acting as antigen presenting cells
what are immunoglobulins
antibodies produced by B-cells and plasma cells
what are immunoglobulins made up of
proteins
2 heavy chains (u, alpha, delta, gamma, epsilon)
2 lights chains (K or lambda)
which immunoglobulins are monomeric
IgD
IgE
IgG
which immunoglobulins are dimeric
IgA
which immunoglobulins are pentameric
IgM
where does initial production and development of B cells occur
in the bone marrow
at what stage of development are B cells when they leave the marrow
immature B cells with Ig on their surface
what do B cells do in the periphery
travel to the follicle germinal centre of the lymph node
identify antigen and improve fit by somatic mutation or deletion
may return to marrow as plasma cell or circulate as memory cell
what do plasma cells do
produce lots of antibodies
what are features of plasma cells
eccentric ‘clock face’ nucleus
open chromatin
plentiful blue cytoplasm
pale perinuclear area
what is the difference between polyclonal and monoclonal
polyclonal cells/antibodies come from many different parent cells
monoclonal cells/antibodies all come from a single precursor
what might cause a polyclonal increase in immunoglobulins
infection
autoimmune conditions
malignancy (reaction of the host to malignant clone)
liver disease
what is another word for monoclonal immunoglobulin
paraprotein
what are monoclonal immunoglobulins a marker of
underlying clonal B-cell disorder
how are immunoglobulins detected/analysed
serum electrophoresis
what is the purpose of serum immunofixation
to classify the abnormal protein band
what are bence jones proteins
immunoglobulin light chains present in urine
how are bence jones proteins detected
urine electrophoresis
are free light chains pathological?
free light chain production of 0.5 g/day is normal
why is there physiological free light chain production
plasma cells produce more light chains than heavy chains so free light chains get secreted into the plasma
are free light chains monomeric or dimeric
kappa light chains are monomeric
lambda light chains are dimeric
what are causes of paraproteinaemia (monoclonal antibodies)
MGUS (asymptomatic) myeloma amyloidosis lymphoma chronic lymphocytic leukaemia
what is myeloma
a plasma cell malignancy
what are direct tumour cell effects of myeloma
bone lesions
increased calcium
bone pain
marrow failure due to replacement of normal marrow
what are paraprotein mediated effects of myeloma
renal failure
immunosuppresion
hyperviscosity
amyloid
what is the most common type of myeloma
IgG
followed by IgA, then bence jones myeloma
how does myeloma cause lytic bone disease
myeloma cells secrete IL-6 which causes osteoblast suppression and osteoclast activation
(also releases calcium)
what are symptoms of hypercalcaemia
stone, bones, abdominal groans and psychiatric moans
thirst, dehydration and renal impairment
how does myeloma cause renal failure
tubular cell damage by light chains
light chain deposition causes cast nephropathy
sepsis, hypercalcaemia, dehydration, drugs
in which part of the nephron does cast nephropathy occur
thick ascending limb of loop of Henle
how does cast nephropathy occur
light chains react with proteins produced in the thick limb of loop of henle to produce insoluble casts that block the nephron
how can cast nephropathy potentially be reversed
hydration
stop nephrotoxic drugs
steroids/chemo to prevent light chain production
how is myeloma managed
combination chemotherapy is the mainstay
steroids, alkylating agents, new agents
examples of alkylating agents
cyclophosphamide
melphalan
examples of new chemotherapy agents used in myeloma treatment
thalidomide
bortezomib
lenalidomide
which myeloma treatment is suitable for fit patients
high dose chemo and autologous stem cell transplant
what is used to monitor response to myeloma treatment
paraprotein level
what are the steps involved in autologous haematopoietic stem cell transfer
administer pre-treatment to release blood stem cells from bone marrow into blood stream
collect stem cells and freeze until needed
administer chemo to remove/partially remove immune system
return stem cells by infusion into vein
provide supportive treatment until immune system rebuilds
how are symptoms controlled in myeloma
opiate analgesia
local radiotherapy (pain relief/spinal cord compression)
bisphosphonates (correct hypercalcaemia and bone pain)
vertebroplasty (sterile cement to stabilised fractured bone)
what is MGUS
monoclonal gammopathy of undetermined significance
how is MGUS defined
paraprotein <30 g/l
bone marrow plasma cells <10%
no evidence of myeloma end organ damage
what causes AL amyloidosis
mutation in light chain causing altered structure
results in precipitates forming in tissues as an insoluble beta pleated sheet
how is AL amyloidsis treated
chemo to switch of light chain supply
which organs can be damaged in AL amyloid
kidney: nephrotic syndrome
heart: cardiomyopathy
liver: organomegaly and deranged LFTs
neuropathy: autonomic/peripheral
GI tract: malabsorption
how is amyloid diagnosed
congo red stain on organ biopsy (rectal or fat biopsy is less invasive)
evidence of deposition in other organs
SAP scan
echo/cardiac MRI
nephrotic range proteinuria
what does a SAP scan do
radio-labelled serum amyloid P localises rapidly and specifically to amyloid deposits in proportion to the quantity of amyloid present
what are SAP scan used for
monitor disease burden and treatment response
what is the buzzword for amyloid in Congo red staining
‘apple-green’ birefringence under polarised light
what cells are affected in Waldenstrom’s macroglobulinaemia
clonal disorder of cells intermediate between a lymphocyte and a plasma cell
which Ig is produced in Waldenstrom’s macroglobulinaemia
IgM
pentameric = large = macroglobulin
what are clinical features of waldenstrom’s
hyper viscosity syndrome: fatigue, visual disturbance, confusion, coma, bleeding, cardiac failure
night sweats
weight loss
how is waldenstrom’s treated
chemo plasmapheresis (removes paraprotein from the circulation)
