Paraprotein Disease Flashcards by Martha Innes

What are plasma cells?

Antibody factories that produce lots of antibodies in response to antigen presentation

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What do plasma cells look like?

Open chromatin
Blue cytoplasm
Pale perinuclear area
Look like blue fried eggs

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What is the structure of antibodies?

2 heavy chains
2 light chains
Constant region
Variable region

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What are the types of light chain?

Kappa

Lambda

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What is the purpose of the variable region in antibodies?

Allows specificity in binding to antigens

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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

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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

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What is monoclonal expansion known as?

Paraprotein disease

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What situations does polyclonal expansion occur in?

Infection
Malignancy
Autoimmune disease

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What is the immunoglobulin produced excessively in monoclonal expansion known as?

A paraprotein

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What are causes of paraprotein disease?

Myeloma
MGUS
AL amyloidosis
Waldenstrom's macroglobinaemia
B cell lymphoma
Chronic lymphocytic leukaemia

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What will paraprotein disease show on blood film, and what does this look like?

Rouleaux formation

Stacking of blood cells

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What is myeloma?

Malignant proliferating fo plasma B cells in the bone marrow

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How is myeloma classified?

Based on the class of antibody and type of light chain produced
IgG, IgA
Kappa, lambda

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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

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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

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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