Myeloma & other plasma cell dyscrasias Flashcards
what is the function of B cells:
- derived from?
- belong to what part of immune system?
- roles?
-Derived from pluripotent haematopoietic stem cells
Part
- adaptive immune system
- antibody production and act as antigen presenting cells
What are immunoglobulins?
- composed of what?
- name the different immunoglobulins and describe their structure
- antibodies produced by B cells and T cells
- proteins made up of 2 heavy and 2 light chains
-Monomer IgD, IgE, IgG
Dimer, IgA
Pentamer, IgM
B cell development
- where does initial development occur?
- what influences the variable nature of the Ig variable element?
- What antigens are expressed on B cell surface?
- what do plasma cells do?
- in the BM
- it is generated from V-D-J region recombination in early development
- CD19+ and CD20+
- they secrete antibody
Describe the path of B cells after they leave the BM?
travel to the follicle germinal
centre of the lymph node
identify the antigen and improve fit by somatic
mutation or be deleted
returns to marrow either as plasma cell OR memory cell in circulation
Plasma cell
- function?
- appearance on H&E
-secretes antibody
-eccentric clock face nucleus
open chromatin due to synthesising mRNA
plentiful blue cytoplasm
pale perinuclear area
definition of :
- Polyclonal antibodies
- Monoclonal antibodies
- what triggers a polyclonal increase in Ig? commonly what virus?
- What triggers a monoclonal rise in Ig?
- what is the name for a monoclonal Ig?
- how are Ig’s detected
- How are paraproteins detected?
- how are abnormal proteins classified?
- secreted by different B cell lineages within the body
- come from clonal expansion of a single B cell lineage
- reactive response to infection, autoimmune, malignancy, liver disease, commonly HIV
- Marker of an underlying B cell disorder, not normally present
- paraprotein
-via serum electrophoresis
separated serum proteins appear as distinct bands
Ig’s are located in the gamma region
- there will be a distinct band in the gamma region
- via serum immunofixation
What are Bence-Jones proteins?
- Why are they present?
- how are they detected?
- present in what disorder?
They are free immunoglobulin light chains
- if there is polyclonal or monoclonal increase in the no. of plasma cells then the amount of free light chains in the plasma increases
- detected via urine electrophoresis
- Any clonal B cell disorder, most commonly MGUS
Myeloma
- what is it?
- what effects does it have on the body? (2 main driving factors)
- how is myeloma classified?
- characterisitc on Xray?
-malignancy of plasma cells
-direct tumour effects bone lesions-lytic bone disease hypercalcaemia bone pain replace normal BM leading to BM failure & pancytopenia
Paraprotein mediated effects renal failure immunosuppression hyperviscoscity amyloid
- according to type of antibody produced, IgG most common
- Lytic bone disease giving pepper pot skull
Why does lytic bone disease occur in myeloma?
plasma cells take over the BM and shift the balance in bone turnover
They release increased IL 6 which encourages proliferation of Myeloma cells but also down regulation of osteoblasts and up regulation of osteoclasts causing increased bone destruction
this also explains why Ca 2+ levels increase
Give the symptoms of hypercalcaemia? (7)
stones bones abdominal groans psychiatric moans thirst dehydration renal impairment
Myeloma and the kidney
-name the different mechanisms by which myeloma can cause kidney damage? (6)
- tubular cell damage by light chains, light chain deposition leads to cast nephropathy
- sepsis can cause damage
- hypercalcemia + dehydration
- drugs e.g. NSAIDS
- amyloid
- hyperuricaemia
Explain how cast nephropathy occurs?
-how is it managed?
-free light chains can be filtered through the glomerular pores and have a half life in the serum of 2-6 hrs.
The proximal tubule reabsorbs the light chains.
if the proximal tubule is overwhelmed the light chains pass into the loop of Henle.
Here an insoluble Tamm-Horsfall protein is produced and this can combine with free light chains to produce insoluble casts.
-may be reversible with prompt treatment, use steroids or chemo to switch off light chain production
Myeloma treatment
- describe the treatment regime used?
- how is response measured?
- how are symptoms controlled? (pain, spinal cord compression, hypercalcaemia, bone pain, fractured bone)
-corticosteroids; dexamethasone or prednisolone
alkylating agents (chemo) e.g. cyclophosphamide, melphalan,
Novel agents e.g. thalidomide
High dose chemo/autologous stem cell transplant in fit patients
-opiate analgesia (avoid NSAIDs)
local radiotherapy, compression
Bisphosphonates
Vertebroplasty
What is the definition of MGUS?
Monoclonal Gammopathy of uncertain significance
-Paraprotein <30 g/l
BM plasma cells <10%
+ no evidence of myeloma end organ damage i.e. Normal Ca, Normal renal function, Normal Hb, No lytic lesions, no inc in infection
Describe the process of AL amyloidosis?
- clinical effect of increased levels of amyloid on kidney, heart, liver, NS, GI?
- how is AL amyloidosis Dx & staged? (6)
- what is seen on biopsy under polarise light?
mutation in the light chains leads to altered structure so they precipitate in tissues as an insoluable beta pleated sheet
Accumulation in the tissues causes organ damage
its a slowly progressive multi system disease
-nephrotic syndrome cardiomyopathy organomegaly and deranged LFTs autonomic & peripheral neuropathy Malabsorption
-organ biopsy
use congo red stain
rectal/fat biopsy if highly suspicious
+ SAP scan, echocardiogram and heavy proteinuria
-apple green birefringence
