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Haematology and Immunology > Myeloma > Flashcards

Myeloma Flashcards

1
Q

What is antibodies produced by?

A

B cells

mostly plasma cells

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2
Q

Primary role of antibodies

A

To recognise and bind to pathogens

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3
Q

How do antibodies recognise and bind to pathogens?

A

They may directly impede a biological process or

Direct other compounds of the immune system by ‘tagging’ the antigen

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4
Q

What is the Fab region of the antibody?

A

Variable

Defines target binding

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5
Q

What is the Fc region of the antibody?

A

Constant

defines subclass

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6
Q

What is the shape of an antibody?

A

Y shaped

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7
Q

What are the 5 different types of the 2 heavy chains of antibodys?

A 
IgG 
IgA
IgM 
IgD
IgE
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8
Q

Which isotope of antibodies is the most prevalent?

A

IgG

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9
Q

What does IgA do?

A

Mucous membrane immunity

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10
Q

What is IgM involved with?

A

Initial phase of Ab production

Exist as a pentamer with high molecular weight so viscous

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11
Q

2 light chains of antibodies

A

Kappa

Lambda

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12
Q

Serum immunoglobulin total level involves….

A

Measuring Ig subclasses by heavy chain/Fc section
Electrophoresis and immunofixation
Serum light chain levels / urine Bench Jones protein

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13
Q

What does electrophoresis do?

A

Assesses antibody diversity and identifies paraprotein
separates protein based on size and charge
Forms a characteristic pattern of bands of different widths and intensities based on protein present
- paraprotein or monoclonal band

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14
Q

What does a paraprotein appear as on electrophoresis?

A

A spike

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15
Q

If the same Ig is found in a region, what is this known as?

A

Paraprotein

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16
Q

What does immunofixation do?

A

Identifies which class of paraprotein is present i.e. IgG, IgM

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17
Q

What does serum light chain levels / urine bench jones protein look at?

A

Assess imbalance / excess of light chains in urine or serum

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18
Q

Features of paraprotein and what does it tell us?

A

Monoclonal immunoglobulin present in blood or urine (should all be different)
If present tells us that there is monoclonal proliferation of a B lymphocyte / plasma cell somewhere in the body

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19
Q

What should be done to identify a paraprotein?

A

Electrophoresis

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20
Q

What are IgM paraproteins found in?

A

Lymphoma

Maturing B lymphocytes make IgM antibody at the start of the immune response

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21
Q

What are IgG and IgA paraproteins found in?

A

Myeloma

Mature plasma cells generate these types of immunoglobulin after isotope switching

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22
Q

What is myeloma?

A

Neoplastic disorder of the plasma cells (abnormal plasma cells) in bone, resulting in excessive production of a single type of immunoglobulin (paraprotein)

23
Q

Who is myeloma most commonly seen in?

A

Elderly

Black

24
Q

Presentation of myeloma

A 
CRAB
- raised calcium 
- renal failure 
- anaemia (bone marrow failure) - lethargy 
- bone lesions 
Bone disease 
- lytic bone lesions
- osteoporosis leading to pathological fractures
- cord compression
- bone pain
Infections (lack of normal Ig)
Amyloidosis
25
Q

Effects of paraprotein in myeloma

A 
Renal failure
- cast nephropathy 
- immunoglobulin deposit in renal tubules blocking it (light chains clogging up the kidneys) 
Hyper viscosity 
- increased blood viscosity
- impaired microcirculation 
- Hypoperfusion 
- bleeding - retinal, oral, nasal, cutaneous 
Hypogammaglobulinaemia 
- impaired production of normal IgG
- tendency to infection 
Amyloidosis
- AL amyloid if caused by light chain or paraprotein 
- nephrotic syndrome
- cardiac failure (LVH)
- carpal tunnel syndrome
- autonomic neuropathy 
- cutaneous infiltration
26
Q

What is amyloidosis?

A

A group of diseases characterised by the deposition of fibrillary protein

27
Q

How do you get rid of paraprotein?

A

Chemotherapy

28
Q

Pathology of myeloma

A

Excess plasma cells in bon marrow >10%

Paraproteins common

29
Q

Types of paraprotein in myeloma

A

IgG myeloma = 55%
IgA myeloma = 21%
Light chain only = 22%
Other (IgD, non secretory)

30
Q

Stage of myeloma is based on what?

A

Albumin and beta-2 macroglobulin

  • if albumin goes down, paraprotein goes up
  • beta 2 macroglobulin marker of how fast it is growing
31
Q

Treatment of myeloma

A 
"Watch and wait" until problems arise 
Chemotherapy
Thalidomide 
Bisphosphonate therapy 
RT
Steriods
Surgery (pinning of long bones, decompression of spinal cord)
Autologous stem cell transplants in younger patients
32
Q

Why does IgM myeloma not exist?

A

IgM is made by the B lymphocytes not the plasma cells

33
Q

What are IgM paraproteins associated with?

A

Low grade lymphomas

34
Q

Clinical presentation of IgM paraproteins

A 
Bone marrow failure
- anaemia
- thrombocytopenia 
Lymphadenopathy 
HSM
B symptoms
35
Q

Why are immunoglobulins usually made?

A

In response to an antigen

36
Q

The making of immunoglobulins causes what to happen?

A

Clonal reproduction of plasma cells which release the same immunoglobulin to destroy the antigen

37
Q

What is the most common immunoglobulin produced in myeloma?

A

IgG

38
Q

Light chains of the immunoglobulins clogging up the kidneys can sometimes lead to what?

A

Amyloid sheet

39
Q

Why is it vital to look at urine electrophoresis and serum?

A

Excess light chains have low molecular weight and they are often not detected by serum protein electrophoresis

40
Q

What are the light chains found in urine called?

A

Bence Jones protein

41
Q

Diagnosis for myeloma - must have 2 out of 3 for

A

Lytic bone lesions
Excess plasma cells in marrow
Serum paraprotein or urinary bence jones protein

42
Q

What is monoclonal gammopathy of uncertain significance? (MGUS)

A

5% of people > 60 years old have a paraprotein

The vast majority are asymptomatic and will go onto develop myeloma

43
Q

Overall survival of myeloma

A

7 years

44
Q

Side effects of chemotherapy

A 
Toxic to dividing cells
- hair
- GI 
- skin 
- blood 
- mucositis 
Nausea and vomiting 
Tumour lysis syndrome 
Bone marrow failure (neutropenic sepsis)
Hyperuricaemia 
Specific drug side effects e.g. pulmonary fibrosis (busulphan)
Secondary malignancy
45
Q

What KEY blood results should be looked at in myeloma?

A

Total proteins

Albumin

46
Q

CRABI numonic for remembering symptoms of myeloma

A 
Hypercalcaemia
Renal disease
Anaemia
Bone problems (overactivity of osteoclasts)
Immunoglobulins
47
Q

What features of a presentation would point towards a diagnosis of multiple myeloma?

A

Hypercalcaemia
Renal failure
High total protein

48
Q

Investigations of multiple myeloma

A

Monoclonal proteins (IgA or IgG) in the serum
Urine Bench Jones Protein
Increased plasma cells in the bone marrow
Skeletal survey - for lytic bone lesions
X ray
- rain drop skull

49
Q

What criteria is needed to diagnose multiple myeloma?

A

One major and one minor needed OR three minor who has signs of symptoms

50
Q

Major criteria for multiple myeloma

A

Plasmacytoma (biopsy)
30% plasma cells in bone marrow
Elevated levels of M protein in blood or urine

51
Q

Minor criteria for multiple myeloma

A

10 - 30% plasma cells in bone marrow
Minor elevations of M protein in blood or urine
Osteolytic lesions on imaging
Low levels of Abs (not produced by cancer cells) in the blood

52
Q

Pathology of the hypercalcaemia present in myeloma

A

Primary factor
- increased osteoclastic bone resorption caused by local cytokines released by the myeloma cells
Much less common contributing factors
- impaired renal function
- increased renal tubular calcium reabsorption
- elevated PTH-rP levels

53
Q

What can precipitate renal failure in patients with myeloma?

A

NSAIDs

54
Q

What would multiple myeloma look like on blood film?

A

Rouleaux formation

Haematology and Immunology (18 decks)

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