Plasma Cell Dyscrasias Flashcards
B cells are derived in the _________ from ________
Bone marrow
Haematopoeitic stem cells
What is the dual role of B cells in the immune system?
Antibody production
Acts as antigen presenting cells
What are immunoglobulins?
Antibodies produced by B cells and plasma cells, that recognize a specific antigen
Describe the structure of an immunoglobulin
Two heavy chains
Two light chains
An Ig variable element at the end of each chain
B cells in the lymph node return to the plasma after picking up an antigen. What two cells can they transform into?
Plasma cells
Memory B cells
What is the role of a plasma cell?
A fully differentiated B cell that pumps out antibody
List key features of the histological appearance of plasma cells
Eccentric ‘clock face’ or ‘fried egg’ nucleus
Blue cytoplasm (containing protein)
Coarse chromatin pattern (mRNA synthesis)
Pale perinuclear area (Golgi apparatus)
What is the clinical marker of a clonal B cell disorder?
Monoclonal immunoglobulin (single B cell expansion)
What is a paraprotein?
An abnormal immunoglobulin fragment that is produced in excess by an abnormal monoclonal proliferation of plasma cells
How are abnormal protein bands on immunoglobins detected?
Serum electrophoresis
How are abnormal protein bands classified after they have been detected?
Serum immunofixation
What us a Bence Jones protein?
A monoclonal globulin protein or immunoglobulin light chain found in urine electrophoresis
What is the pathogenesis behind multiple myeloma?
Abnormal plasma cell proliferation due to genetic hits causing chromosomal translocation and mutation
What are the clinical features of multiple myeloma?
TUMOUR EFFECTS
Bone lesions
Bone pain
Hypercalcaemia (stones, bones, abdominal groans, psychic moans)
PARAPROTEIN EFFECTS Renal failure Immune suppression Hyperviscosity Amyloidosis
Explain why osteolytic lesions are a characteristic feature of multiple myeloma
IL6 produced by plasma cells activates osteoclasts causing bone resorption and hypercalcaemia and suppresses osteoblasts
Why does multiple myeloma lead to renal failure?
Tubular cell damage by deposition of light chains causing cast nephropathy
Outline treatment of multiple myeloma
Stop nephrotoxins
Combination chemotherapy (switch off light chains)
CCS e.g. dexamethasone, prednisolone
Alkylating agents e.g. cyclophosphonamide
High dose chemo/stem cell transplant in fit patients
Outline symptom control in multiple myeloma
Opiate analgesia (avoid NSAIDs) Local radiotherapy (pain relief or cord compression) Biphosphonates (correct hypercalcaemia and pain) Vertebroplasty (inject sterile cement into fracture)
List the characteristic features of monoclonal gammopathy of undetermined significance
Paraprotein <30g/l
Bone marrow plasma cells <10%
No evidence of myeloma end organ damage (normal calcium, renal function, Hb, bones, immune system)
MGUS is at risk of progression to which haematological malignancy?
Multiple myeloma
What is AL amyloidosis?
Rare disorder characterised by a mutation in light chain leading to altered structure and formation of insoluble beta pleated sheats that can accumulate in the body, causing organ damage
List features of organ damage found in AL amyloidosis
Nephrotic syndrome Cardiomyopathy Hepatomegaly Neuropathy Malabsorption
Outline investigations used to diagnose AL amyloidosis
Organ biopsy to confirm amyloid deposition via stain
SAP scan to localise amyloid deposits
Echo/cardiac MRI
Nephrotic range proteinuria
State the characteristic clinical feature of a stained organ biopsy containing amyloid protein, and a biopsy placed under polarised light respectively
Congo red
Apple-green birefringence
