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Haematology week 2 > Myeloma and other plasma cell disorders > Flashcards

Myeloma and other plasma cell disorders Flashcards

1
Q

What are the 2 main functions of B lymphocytes ?

A
  1. Antibody production - this is the main function we really need to know about
  2. Can also act as antigen presenting cells
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2
Q

What are immunoglobulins and what are the different types in the body?

A

Antibodies produced by B-cells and plasma cells

The different types are:

  1. IgE
  2. IgD
  3. IgG
  4. IgA
  5. IgM
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3
Q

What does an antibody (immunoglobulin) do ?

A

It recognises and attachs to a specific antigen

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4
Q

Describe the structure of immunoglobulins

A
  • They are proteins made up of 2 heavy chains and 2 light chains
  • The terminal ends of the polypeptide chains show considerable variation in amino acid composition and are termed the variable regions
  • The variable regions of heavy and light chains compose the antigen binding sites of the immunoglobulins

Be able to point out the Fab and Fc regions also

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5
Q

Where are the 5 different antibodies mainly found ?

A
  1. IgA - second most common human immunoglobulin in serum. It is secreted in milk and is also in secretions (e.g. tears, saliva and mucous).
  2. IgD function is relatively unknown
  3. IgE is involved in involved in allergic reactions
  4. IgG - most common immunoglobulin, involved in the secondary immune response to infections etc
  5. IgM - involved in the primary immune response e.g. ABO incompatability
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6
Q

Which immunoglobulin can cross the placenta ?

A

IgG

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7
Q

What is the overall structure of the 5 different antibodies

A
  • Monomers - IgD, IgE, IgG
  • Dimer - IgA
  • Pentamer - IgM
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8
Q

Describe the development of B cells

A
  1. Initial production and development occurs in the bone marrow
  2. VDJ recombination occurs and results in the highly diverse repertoire of antibodies/immunoglobulins found on B cells, this occurs in the bone marrow and results in the generation of the variable region on immunoglobulin (Ig), any self reactive cells will be removed
  3. Immature B cells with Ig on their surface exit the bone marrow into the periphery to meet their target
  4. In the periphery they travel to the follicle germinal centre of lymph nodes
  5. Here they identify their target antigen and improve their fit for it by somatic mutation or be deleted
  6. May return to the marrow as plasma cell or circulate as memory cell
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9
Q

What is the typical appearance of plasma cells ?

A
  1. Open chromatin - Synthesising mRNA
  2. Plentiful blue cytoplasm - Laden with protein
  3. Pale perinuclear area - Golgi apparatus

Typical fried egg appearance

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10
Q

What is the function of a plasma cell ?

A

It pumps out antibody

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11
Q

What are the causes of a polyclonal increase in immunoglobulins ?

A

Reactive:

  • Infection
  • Autoimmune
  • Malignancy- reaction of the host to the malignant clone
  • Liver disease
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12
Q

What happens in myeloma ?

A

There is an abnormal prolfieration of a single clone (monoclonal) of plasma cells leading to secretion of immmunoglobulin (Ig) and Ig fragment (light chains on their own called paraproteins), causing the dyfunction of many organs esp the kidneys

Monoclonal rise in Immunoglobulins produced in high amounts are usually either IgG or IgA, the other immunoglobulins are produced in low amounts

Paraproteins often seen in the urine - free light chains of kappa or lambda type

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13
Q

What test is done to identify immunoglobulins ?

A

Serum electrophoresis

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14
Q

How are paraproteins detected and what are they referred to as?

A

They are detected on urine electrophresis

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15
Q

What are the BJP proteins detected on urine electrophoresis and what is the normal production of light chains ?

A

The normal production of light chains is 0.5g/day as when immunoglobulins are produced there is excess light chains produced.

If there is an increase in the number of plasma cells e.g. reactive cause due to infection or a monoclonal cause e.g. multiple myeloma there will be an increased number of excess light chains produced

The excess light chains can then leak into the urine as BJP

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16
Q

What are the main causes of paraproteinuria ?

A
  1. MGUS - the most common
  2. Myeloma
  3. Amyloid
  4. Waldenstrom’s Macroglobulinaemia
  5. (IgM paraprotein)
17
Q

What are the symptoms of mutiple myeloma ?

A

Osteolytic bone lesions (due to increased osteoclast activation) causing:

  • backache,
  • pathological fractures e.g. of long bones and ribs
  • vertebral collapse

Hypercalcaemia

Bone marrow infiltration: (marrow failure)

  • Anaemia
  • Infection
  • Bleeding

Recurrent infections due to immuneparesis (reduction in the levels of at least 1/2 immunoglobulins) and also because of neutropenia

Renal impairment - due to light chain deposition (paraproteins)

Think - CRABBI (calcium, renal, anaemia, bleeding, bones, infection)

18
Q

How is myeloma classified ?

A
  • Based on the type of antibody produced
  • Multiple myeloma patients can be classified on the basis of the type of monoclonal protein they produce. The majority of patients (59%) produced IgG monoclonal proteins, 21% produced IgA, 15% just free light chains and 3% did not have any serum or urine monoclonal proteins detected.
19
Q

What characterisitc feature is shown and what condition can cause this ?

A

Multiple myeloma - shows lytic bone lesions causing a characterisitc pepper pot appearance

20
Q

What condition can this be caused by?

A

Multiple myeloma

21
Q

How do lytic bone lesions arise in multiple myeloma ?

A

Due to increased activation of osteoclasts and underactivation of osteoblasts

22
Q

What are the symptoms of hypercalcaemia associated with multiple myeloma ?

A
  • Stones
  • Bones
  • Abdominal groans
  • Psychiatric moans
  • Thirst
  • Dehydration
  • Renal impairment
23
Q

How common is renal impairement in patients with myeloma and what is the common cause of it ?

A
  • Roughly 30% will get renal impairement
  • Tubular cell damage due to light chain deposition
  • May see cast nephropathy which is light chains shed in the urine
24
Q

What are the characterisitic test findings in mutliple myeloma ?

A
  • FBC - shows a normocytic normochromic anaemia
  • Blood film may show rouleaux formation
  • Often increased Ca
  • Increased Urea and Cr - due to renal impairment
  • Bone marrow aspirate and biopsy would show plasma cell infiltration
25
Q

How is multiple myeloma diagnosed ?

A

Using serum and urine electrophoresis - monoclonal protein band on serum seen of paraproteins

26
Q

What invesitgation should you do following a diagnosis of multiple myeloma ?

A

Skeletal survey to detect bone disease - X-rays of chest, spine, skull and pelvis

27
Q

Who most commonly gets multiple myeloma ?

A

Older people - median age is 65

28
Q

What is the treatment of multiple myeloma ?

A
  1. Corticosteroids; dexamethasone or prednisolone
  2. Alkylating agents eg cyclophosphamide, melphalan
  3. May also add thalidomide, , bortezomib, or lenalidomide

High dose chemo/autologous stem cell transplant in fit patients

29
Q

What is the treatment for symptoms in multiple myeloma ?

A
  1. Opiate analgesia (avoid NSAIDs)
  2. Local radiotherapy - good for pain relief or spinal cord compression
  3. Bisphosphonates - corrects hypercalcaemia and bone pain
  4. Vertebroplasty – inject sterile cement into fractured bone to stabilise

Haematology week 2 (17 decks)

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