Paraprotein Disease Flashcards
What are plasma cells?
Antibody factories that produce lots of antibodies in response to antigen presentation
What do plasma cells look like?
Open chromatin
Blue cytoplasm
Pale perinuclear area
Look like blue fried eggs
What is the structure of antibodies?
2 heavy chains
2 light chains
Constant region
Variable region
What are the types of light chain?
Kappa
Lambda
What is the purpose of the variable region in antibodies?
Allows specificity in binding to antigens
What are free circulating light chains?
Production of light chains is slightly higher than production of heavy chains, so some light chains circulate freely in the body
What is the difference between polyclonal and monoclonal expansion?
Polyclonal is the expansion of a variety of B cell populations
Monoclonal is the expansion of a single B cell population
What is monoclonal expansion known as?
Paraprotein disease
What situations does polyclonal expansion occur in?
Infection
Malignancy
Autoimmune disease
What is the immunoglobulin produced excessively in monoclonal expansion known as?
A paraprotein
What are causes of paraprotein disease?
Myeloma MGUS AL amyloidosis Waldenstrom's macroglobinaemia B cell lymphoma Chronic lymphocytic leukaemia
What will paraprotein disease show on blood film, and what does this look like?
Rouleaux formation
Stacking of blood cells
What is myeloma?
Malignant proliferating fo plasma B cells in the bone marrow
How is myeloma classified?
Based on the class of antibody and type of light chain produced IgG, IgA Kappa, lambda
What pathophysiological effect does myeloma have on bone?
Breakdown of bone - erosion by up regulation of osteoclast activity and downregulation of osteoblasts - formation of osteolytic lesions - hypercalcaemia Infiltration of marrow - marrow failure
What pathophysiological effect does myeloma have due to antibody and light chain effects?
Increased production of antibodies
- hyperviscocity
- immunosuppression due to failure to produce normal antibodies
Glomerular disease
- deposition of light chains in the kidney causing cast nephropathy and decline in renal function
Amyloid
What is the median age at diagnosis of myeloma?
65-70
What is the presentation of myeloma?
Bone pain (back, worse at night) Pathological fractures Spinal cord compression Hypercalcaemia - stones, bones, groans, thrones, psychiatric moans Anaemia symptoms Bleeding Bruising Recurrent infections Reduced vision Reduced cognition
What are the symptoms of hypercalcaemia?
Stones - renal stones and other renal disease
Bones - bone pain
Groans - abdominal pain
Thrones - thirst, polydipsia, constipation
Psychiatric moans - depression, anxiety
What causes the reduced vision and cognition in myeloma?
Hyperviscocity
What do bloods show in myeloma?
Raised ESR
U&Es - reduced renal function
Hypercalcaemia
Normochromic normocytic anaemia
How is myeloma diagnosed?
Serum electrophoresis showing paraprotein
Diagnosis confirmed on bone marrow aspirate and trephine biopsy
What can be seen by urine electrophoresis in myeloma?
Bence Jones protein
What can be seen on skeletal survey in myeloma?
Pepper-pot skull
Vertebral collapse
What are management options in myeloma?
Dexamethasone Thalidomide Melphalan, cyclophosphamide Monoclonal antibodies - daratumumab High dose chemotherapy/autologous stem cell transplant (AHSCT) in fit patients
What is used to monitor response to myeloma treatment?
Paraprotein
What is used for symptomatic control of bone pain in myeloma?
Analgesia (opiates - avoid NSAIDs)
Bisphosphonates
What is monoclonal homeopathy of unknown significance (MGUS)?
Paraproteinaemia without pathological consequences
Can progress to myeloma
What is the definition of MGUS?
<30g paraprotein
Bone marrow plasma cells <10%
No evidence of myeloma or end organ damage
What tests need to be done to exclude myeloma or end organ damage to diagnose MGUS?
Calcium Hb U&Es Bone scans Make sure no increase in systemic infections
What is the presentation of MGUS?
Usually asymptomatic
10-30% have demyelinating neuropathy
What is AL Amyloidosis?
Group of disorders characterised by production of abnormal light chains from B cell clonal population
What is the pathophysiology of AL amyloidosis?
Abnormal light chains precipitate into tissues and form insoluble beta-amyloid sheets
The amyloid sheets develop in multiple organs and cause multiple end organ damage
Can be primary or secondary to myeloma or Waldenstrom’s
What is the disease pattern of AL amyloidosis?
Slowly progressive
Multisystem disease
What is the presentation of AL amyloidosis?
Nephotic syndrome Hepatosplenomegaly Macroglossia Malabsorption Restrictive cardiomyopathy, sudden death Autonomic and peripheral neuropathy Periorbital purpura (characteristic)
What is a diagnostic sign of AL amyloidosis?
Apple green birefringence with congo red stain on organ biopsy of affected tissue or rectum/fat
What do blood tests show in AL amyloidosis?
Deranged LFTs, U&Es, etc
What is the management of AL amyloidosis?
Chemotherapy to attempt to switch of light chain supply
What is Waldenstrom’s macroglobinaemia?
IgM paraproteinaemia caused by expansion of a cell population intermediate between a plasma cell and lymphocyte - lymphoplasmacytoid neoplasm
What is the presentation of Waldenstrom’s macroglobinaemia?
Hyperviscocity - fatigue - confusion - reduced cognition - visual disturbances - chest and abdominal pain B symptoms - weight loss - night sweats - splenomegaly - lymphadenopathy
What do investigations show in Waldenstrom’s macroglobinopathy?
Raised ESR
IgM paraproteinaemia on electrophoresis
What is the management of Waldenstrom’s macroglobinopathy?
Chemotherapy - chlorambucil
Hyperviscocity - leukapheresis or plasmapheresis
