Myeloma and Plasma Cell Disorders Flashcards
how are B cells made
derived in bone marrow from pluripotent haematopoietic stem cells
self reactive cells are removed
what roles do B cells have
antibody production
acting as antigen presenting cells
what are immunoglobulins
antibodies produced by B cells and plasma cells
made up of 2 heavy chains and 2 light chains
each recognises a specific antigen
how to immunoglobulins exit the bone marrow
immature B cells with immunoglobulin on their surface axis bone marrow ready to meet their target
what do B cells do in the peripheral
travel to the follicle germinal centre of the lymph node
identify the antigen and bind (somatic nutation for a better fit or get deleted if dont fit)
what happens to B cells after they have bound to antigens in the lymph nodes
may return to marrow as PLASMA cell
may circulate as a memory B cell
what does a plasma cell do
‘factory cell’
pumps out antibodies
characteristics of a plasma cell (histological)
eccentric ‘clock face nucleus’
open chromatin synthesising mRNA
lots of blue cytoplasm (full of proteins)
pale perinuclear area (Golgi apparatus)
what is a polyclonal increase in immunoglobulins
lots of immunoglobulins produced by different plasma cells
what do polyclonal immunoglobulins react to
infection
autoimmune
malignancy
liver disease
what is a monoclonal increase in immunoglobulins
lots of immunoglobulins produced all from the same plasma cell
identical antibody structure and specificity
what is a monoclonal immunoglobulin called
Paraprotein
a marker of underlying B cell disorder
what test is done to detect immunoglobulins
serum electrophoresis (detects abnormal protein bands)
what are free light chains found in circulation
because then immunoglobulins are synthesised there are more light chains than heavy chains
the free light chains are secreted into the plasma along with the immunoglobulins
how many free light chains are normally produced per day by plasma cells
0.5g
what can cause the amount of free light chains to increase
if there is a polyclonal increase in plasma cell numbers (infection)
OR
a monoclonal increase in plasma cells (myeloma)
the free chains overflow into the urine and present as Bence Jones proteins (BJP)
what are the causes of paraproteinaemia (monoclonal antibodies)
Monoclonal Gammopathy of undetermined significance
Myeloma
Amyloidosis
Lymphoma
Asymptomatic myeloma
Solitary or extra medullary plasmacytoma
chronic lymphocytic leukaemia
others
what is myeloma
a plasma cell malignancy
how does myeloma occur
Normal plasma cell
mutation occurs
Monoclonal gammopathy of undetermined significant (benign premalignant phase)
more mutations
asymptomatic myeloma occurs (malignant with no organ damage)
myeloma (malignant)
how does myeloma affect the body
produces clonal plasma cells which causes
direct tumour cell effects
- bone lesions
- increased calcium
- bone pain
- replaces normal bone marrow leading to MARROW FAILURE
paraprotein mediated effects
- renal failure
- immune suppression
- hyper viscosity
- amyloid
how is myeloma classified
by the type of antibody produced by the monoclonal plasma cells
IgG - most common IgA Bence Jones myeloma (free light chains) non-secretory myeloma biclonal IgD IgE (v rare)
what does lytic bone disease in myeloma look like
multiple ‘punched out’ lesions in skull
how does myeloma cause lytic bone disease
myeloma cells activate osteoclasts in the marrow and suppress osteoblasts
this causes lytic bone disease and increases Ca causing hyperglycaemia
how does hypercalcaemia present
stones bone abdominal groans psychiatric moans thirst dehydration renal impairment
how does myeloma damage the kidneys
tubular cell damage by light chains
light chain deposition - cast nephropathy
sepsis
hypercalcaemia and dehydration
Drugs, NSAIDS
hyperuricaemia
amyloid
