Myeloma and Other Plasma Cell Disorders Flashcards
what are B cells derived from
pluripotent haematopoietic stem cells in the bone marrow
what is the roles of B cells
part of the adaptive immune system
- 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
Each antibody recognizes a specific antigen
what are the monomer shaped immunoglobulins
IgD
IgE
IgG
what are the dimer shaped immunoglobulins
IgA
what is the pentamer shaped immunoglobulin
IgM
what is the normal pathway of lymphocyte maturation
stem cell»_space; lymphoid progenitors»_space; Pro B cells (IgM)»_space; Pre B cells (IgM & IgD)»_space; IgM B cells
what do IgM B cells divided to make normally
IgM plasma cells
IgA
IgE
IgG
what does IgG eventually go on to become
plasma cells
what is the function of a plasma cell
to produce large quantities of antibodies when needed
how does the nucleus appear in a plasma cell
“clock face nucleus”
nucleus off to one side, can look like a fried egg
what is meant when a blood film is described as polyclonal or monoclonal
polyclonal - multiple types of blood cells seen; can be seen as part of normal function
monoclonal - one type of cell seen overwhelming; suggests pathology
what are the causes of a polyclonal increase in immunoglobulins
infection
autoimmune
malignancy
liver disease
what does a monoclonal increase in immunoglobulins imply
implies that the antibody is all identical and produced by a single B cell
what is a monoclonal immunoglobulin also called and what is it a marker of
paraprotein
underlying clonal B-cell disorder
how can you detect immunoglobulins
serum electrophoresis
what area is immunoglobulins seen in
gamma region
what is bence-jones protein (BJP)
excess immunoglobulin light chains leaking into the urine
» paraproteinaemia
detected by urine electrophoresis
what are causes of paraproteinaemia
1st - MGUS (completely harmless)
2st - myeloma
3rd - Amyloidosis
4th - lymphoma
- asymptomatic myeloma
- chronic lymphocytic leukaemia
essentially what is myeloma
clone of a malignant plasma cell
what are direct tumour effects of myeloma
bone lesions
increased calcium
bone pain
bone marrow failure
what are the effects of paraprotein seen in myeloma
renal failure
immune suppression
hyperviscosity
amyloid
how is myeloma classified
by type of antibody produced
what are the most to least common type of myeloma
Most to least:
- IgG
- IgA
- Bence Jones Myeloma
- Nonsecretory
- IgD
- Biclonal
- IgE
what is myeloma’s affect on bone and what is commonly seen on x-ray
lytic bone disease
“punched-out lesions”
Pepper pot skull
what are Sx of hypercalcaemia
Stones Bones Abdominal groans Psychiatric moans Thirst Dehydration Renal impairment
how can myeloma cause kidney failure
free light chains first accumulate in the proximal tubules before entering the loop of Henle.
Here they can combined with Tamm-Horsfall protein to produce insoluble casts blocking the nephron i.e. cast nephropathy
This can lead to renal failure
what is the Tx of myeloma
Chemotherapy with +/- prednisolone +/- Thalidomide or bortezomib or lenalidomide
If asymptomatic may just observe
how is response to Tx monitored in myeloma
paraprotein
what is symptomatic control of myeloma
opiate analgesia
local radiotherapy
biphosphonates - corrects hypercalcaemia
vertebroplasty - stabilises fractured bone
what is MGUS
Monoclonal Gammopathy of Uncertain Significance
what is the definition of MGUS
Paraprotein <30g/l
Bone marrow plasma cells <10%
No evidence of myeloma end organ damage;
- Normal calcium
- Normal renal function
- Normal Hb
- No lytic lesions
- No increase in infections
what is amyloidosis
accumulation of protein in abnormal fibrillar form
- in tissues can cause organ damage
caused by mutations in the light chain
what can amyloidosis cause
nephrotic syndrome
how is amyloid deposition confirmed
congo red staining
- causes “Apple-green” birefringence under polarised light
what is Waldenstrom’s Macroglobulinaemia
Clonal disorder of cells intermediate between a lymphocyte and a plasma cell
Characteristic IgM paraprotein
what are the Sx of Waldenstrom’s Macroglobulinaemia
lymphadenopathy splenomegaly marrow failure hyperviscosity neuropathy
what are features of hyper viscosity syndrome
Fatigue, visual disturbance, confusion, coma Bleeding Cardiac failure Night sweats Weight loss
Tx of WM
chemotherapy plasmapheresis (removes paraprotein from the circulation)
