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Haematology > Myeloma and Paraproteins > Flashcards

Myeloma and Paraproteins Flashcards

1
Q

What cells produce antibodies?

A

Plasma cells (IgM produced by B lymphocytes)

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2
Q

What are the two forms in which Ig can exist?

A

Membrane bound

Soluble

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3
Q

What is the role of antibodies?

A

Recognise and bind to pathogens to be tagged for destruction

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4
Q

What is the basic structure of Ig?

A

Y shaped
2 heavy chains and 2 light chains
Variable and constant domains
Fc and Fab region

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5
Q

What is the constant fraction of Ig useful for?

A

It is a flag for the immune system

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6
Q

What are the five heavy chain types of Ig?

A

IgM, IgG, IgA, IgE, IgD

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7
Q

What is IgM?

A

Initial phase antibody

Exists as pentamer

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8
Q

What is IgG?

A 
Most prevalent antibody subclass
Long lived immunity
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9
Q

What is IgA implicated in?

A

Mucosal membrane immunity

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10
Q

What is IgE involved in?

A

Parasite immune responses

Also implicated in hypersensitivity reactions

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11
Q

What are the two types of light chains?

A

Kappa or lambda

NB one cell will only make 1 type of light chain

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12
Q

Can free light chains be found in the blood?

A

Only at low levels

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13
Q

What does the Fab region determine?

A

It is variable and defines target binding

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14
Q

What does the Fc region determine?

A

Constant and defines subclass

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15
Q

What cells make Ig?

A

Plasma cells

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16
Q

What is normal IgG level?

A

6-15g/L

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17
Q

What is normal IgA level?

A

1-4.5g/L

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18
Q

What is a normal IgM level?

A

0.5-2g/l

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19
Q

What is a paraprotein?

A

A monoclonal Ig present in the blood or urine

20
Q

What does a paraprotein tell us?

A

There is a monoclonal proliferation of a B lymphocyte/plasma cell elsewhere in the body

21
Q

What tests can you do to assess Ig levels?

A

Total Ig levels
Electrophoresis
Immunofixation
Light chains (assessing imbalance/xs in urine/serum)

22
Q

What is electrophoresis?

A

Separation of proteins based on size and charge using an electric current
Spikes may be indicative of a paraprotein

23
Q

What is immunofixation used for?

A

Finding out what class of paraprotein is present (IgG, IgM)

24
Q

What kinds of cells do lymphomas tend to arise from and why?

A

B cells due to germinal centre reaction

25
Q

What occurs in the germinal centre reaction?

A

Each of the cells start with a germline configuration
B lymphocyte chops up DNA to see what variable domains can be made
If it encounters an antigen it binds it and undergoes somatic hypermutation whereby the Ab mutates further to form a v. specific mutation

26
Q

What is an IgM paraprotein indicative of?

A

Lymphoma (as maturing B lymphocytes make IgM)

27
Q

What is an IgA/IgG paraprotein indicative of?

A

Myeloma

mature plasma cells generate these types of Ab after isotope switching

28
Q

What is myeloma?

A

Neoplastic disorder of plasma cells, usually resulting in excessive production of a single paraprotein

29
Q

What age is myeloma most common in?

A

70s

30
Q

What are the clinical features of myeloma?

A 
Lytic bone lesions
Pathological fractures
Cord compression
Hypercalcaemia
Bone marrow failure (anaemia, bleeding, infections) 
Renal failure 
Hyperviscosity 
Hypogammaglobulinaemia
Amyloidosis
31
Q

Why do you get lytic bone disease in myeloma?

A

Osteoclast activation by cytokines

32
Q

Why do you get bone marrow failure in myeloma?

A

Bone marrow becomes overrun with plasma cells

Infections as no normal Ab left in later stages

33
Q

Why do you get renal failure in myeloma?

A

Cast nephropathy

Ig deposition and blockage of renal tubules

34
Q

Why do you get hypogammaglobulinaemia in myeloma?

A

Impaired normal production of Ig

35
Q

What is amyloidosis?

A

Deposition of fibrillar proteins (formed by abnormal folding of proteins to form crystalloid structure)

36
Q

What kind of amyloidosis is caused by light chain/paraprotein deposition?

A

AL amyloidosis

37
Q

What kind of amyloidosis is caused by excess protein from an uncontrolled inflammatory reaction?

A

AA amyloidosis

38
Q

What conditions are associated with AA amyloidosis?

A 
Nephrotic syndrome
Cardiac failure
Carpal tunnel
Autonomic neuropathy (dizziness, diarrhoea) 
Cutaneous infiltration
39
Q

What can result from hyperviscosity?

A

Increased viscosity of blood –> impaired microcirculation and hypoperfusion
Commonly get bleeding as capillaries burst
Can also –> cardiac failure, pulmonary congestion, confusion, renal failure

40
Q

true or false:

Finding paraproteins in serum = myeloma?

A

No, 3-4% of population over 75 have these with no clinical consequences

= monoclonal gammopathy of uncertain significance

41
Q

How do you diagnose myeloma?

A

By finding excess plasma proteins in the bone marrow (>10% of bone marrow)

42
Q

What is the most common type of paraprotein?

A

IgG

43
Q

How do you stage myeloma?

A

Albumin and beta-2 microglobulin

44
Q

How do you treat myeloma?

A

Chemo - proteasome inhibitors, IMiDs (thalidomide), monoclonal antibodies
Bisphosphonates (zoledronic acid)
Steroids
Surgery (pinning of long bones, cord decompression)
Autologous stem cell transplant

45
Q

What are IgM paraproteins associated with?

A

Low grade lymphoma

46
Q

What is the presentation of low grade lymphoma?

A 
Bone marrow failure 
Lymphadenopathy
Hepatosplenomegaly
B symtpoms
Protein related symptoms
Bone disease RARE

Haematology (14 decks)

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