6: Myeloma and other plasma cell disorders Flashcards
What are the functions of B cells?
Antibody production
Antigen presenting cells
What is a terminally differentiated B cell called?
Plasma cell
Every antibody has two ___ chains and two ___ chains.
two light chains
two heavy chains
What shape is IgM?
Pentamer
Big molecule, so tends to cause hyperviscosity when produced in excess (
Where do B cells mature?
Bone marrow
By which process are a large variety of B cells produced in the bone marrow?
VDJ recombination
After B cells leave the bone marrow, where do they go to be exposed to antigens?
Lymph node follicles
Where in the follicle of a lymph node are B cells found?
Germinal centre
In what forms are mature B cells found in the
a) bone marrow
b) circulation?
a) Memory B cells
b) Plasma cells
all other B cells are found in the lymph nodes, waiting to be activated
How do plasma cells look morphologically?
Fried egg appearance
Nucleus off to the side, deep blue cytoplasm, white Golgi apparatus adhered to nucleus
Blood malignancies are (polyclonal / monoclonal).
monoclonal
cells derived from the same dodgy parent cell
What causes normal increases in antibody levels?
Infection
Inflammation
Malignancy
What is meant by a monoclonal increase in antibodies?
Increase in the clone of a SINGLE B CELL
What are monoclonal antibodies also referred to as?
Paraproteins
All the same because they’re all produced by the same clone of plasma cells
Which investigation is used to separate out the different proteins found in a blood sample?
Serum electrophoresis
How does normal serum electrophoresis look?
Variety of bands referring to variety of proteins, none of them abnormally bright
How does serum electrophoresis look if there is a monoclonal increase in antibody levels?
Bands corresponding to paraproteins will be super bright
representing that there’s a ton of them being produced by a single clone of plasma cells
Which type of chain is produced in excess by plasma cells?
Light chains
Light chains are produced in excess by plasma cells.
How are these proteins excreted?
Via urine
What are light chains called when they are produced in excess and excreted via the urine?
Bence Jones protein
A sign of myeloma (and other diseases causing increased paraproteins) found using urine electrophoresis
What is a malignancy of plasma cells called?
Myeloma
What is the benign precursor of myeloma called?
MGUS
Monoclonal gammopathy of unknown significance
What are the clinical features of myeloma?
Hypercalcaemia symptoms: stones, bones, groans, psych moans
Polydipsia
Renal impairment (reduced eGFR, elevated urea and creatinine)
Which types of myeloma are most common?
IgG myeloma
IgA myeloma
What is the course of myeloma?
relapsing
Why does myeloma cause bony lesions?
Inflammatory cytokines cause OSTEOCLAST activation and OSTEOBLAST suppression
Causing widespread degradation (osteoporsis) and focal lesions
Which metabolic disturbance occurs as a result of bone lysis in myeloma?
Hypercalcaemia
bones, stones, groans and psychic moans
What is a system commonly damaged by the light chains produced in myeloma?
Renal
Light chains are directly toxic to the kidneys; produce pink casts
Pink casts seen in myeloma ___ the renal tubules.
block
How is cast nephropathy managed?
Hydration
Stop nephrotoxic drugs (NSAIDs, ACEIs, ARBs, diuretics, gentamicin, metformin)
Immunosuppression to switch off light chain production
How is myeloma treated?
Immunosuppression
Chemotherapy
Monoclonal antibodies for some types
(High dose chemo AND stem cell transplant in young, fit patients)
How is myeloma activity monitored before and after treatment?
Serum paraprotein levels
Which type of analgesia is given to myeloma patients for bony pain?
Opiates
Which drugs are given to treat hypercalcaemia in myeloma patients?
Bisphosphonates
Pathological fractures are a feature of myeloma.
Where do these typically occur?
Spine (crush fractures of vertebrae)
What is MGUS?
Benign increase in paraprotein / plasma cell levels
Can progress to myeloma
What is an abnormal protein which can accumulate in many organs to cause disease?
Amyloid
How is AL amyloidosis treated?
Chemo
How is amyloidosis diagnosed?
Biopsy to prove deposition
SAP scan - nuclear scan to see deposition in other organs
Which specific stain is used in suspected amyloidosis?
What colour does it turn under light exposure?
Congo red
“Apple green”; birefingence
What is an abnormal paraprotein, pentameric in shape, which is produced in rare disease?
IgM
Which disease, related to myeloma, shows an increase in IgM paraprotein?
Waldenstrom’s disease
What are some symptoms of Waldenstrom’s disease?
Hyperviscosity symptoms - fatigue, visual problems, confusion, coma
B symptoms - fever, weight loss, night sweats
How is Waldenstrom’s disease treated?
Chemotherapy - to kill off plasma cells
Plasmapharesis - filtering of blood to remove IgM paraprotein
How does plasmapharesis treat Waldenstrom’s disease?
Blood filtered to remove plasma which contains IgM
Plasma replaced with donor plasma
What effect does paraprotein accumulation have on the blood?
Hyperviscosity
Blood is thicker and cannot oxygenate tissues as effectively
