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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
Effects of paraprotein in myeloma
``` 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
What is amyloidosis?
A group of diseases characterised by the deposition of fibrillary protein
27
How do you get rid of paraprotein?
Chemotherapy
28
Pathology of myeloma
Excess plasma cells in bon marrow >10% | Paraproteins common
29
Types of paraprotein in myeloma
IgG myeloma = 55% IgA myeloma = 21% Light chain only = 22% Other (IgD, non secretory)
30
Stage of myeloma is based on what?
Albumin and beta-2 macroglobulin - if albumin goes down, paraprotein goes up - beta 2 macroglobulin marker of how fast it is growing
31
Treatment of myeloma
``` "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
Why does IgM myeloma not exist?
IgM is made by the B lymphocytes not the plasma cells
33
What are IgM paraproteins associated with?
Low grade lymphomas
34
Clinical presentation of IgM paraproteins
``` Bone marrow failure - anaemia - thrombocytopenia Lymphadenopathy HSM B symptoms ```
35
Why are immunoglobulins usually made?
In response to an antigen
36
The making of immunoglobulins causes what to happen?
Clonal reproduction of plasma cells which release the same immunoglobulin to destroy the antigen
37
What is the most common immunoglobulin produced in myeloma?
IgG
38
Light chains of the immunoglobulins clogging up the kidneys can sometimes lead to what?
Amyloid sheet
39
Why is it vital to look at urine electrophoresis and serum?
Excess light chains have low molecular weight and they are often not detected by serum protein electrophoresis
40
What are the light chains found in urine called?
Bence Jones protein
41
Diagnosis for myeloma - must have 2 out of 3 for
Lytic bone lesions Excess plasma cells in marrow Serum paraprotein or urinary bence jones protein
42
What is monoclonal gammopathy of uncertain significance? (MGUS)
5% of people > 60 years old have a paraprotein | The vast majority are asymptomatic and will go onto develop myeloma
43
Overall survival of myeloma
7 years
44
Side effects of chemotherapy
``` 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
What KEY blood results should be looked at in myeloma?
Total proteins | Albumin
46
CRABI numonic for remembering symptoms of myeloma
``` Hypercalcaemia Renal disease Anaemia Bone problems (overactivity of osteoclasts) Immunoglobulins ```
47
What features of a presentation would point towards a diagnosis of multiple myeloma?
Hypercalcaemia Renal failure High total protein
48
Investigations of multiple myeloma
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
What criteria is needed to diagnose multiple myeloma?
One major and one minor needed OR three minor who has signs of symptoms
50
Major criteria for multiple myeloma
Plasmacytoma (biopsy) 30% plasma cells in bone marrow Elevated levels of M protein in blood or urine
51
Minor criteria for multiple myeloma
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
Pathology of the hypercalcaemia present in myeloma
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
What can precipitate renal failure in patients with myeloma?
NSAIDs
54
What would multiple myeloma look like on blood film?
Rouleaux formation

Haematology and Immunology (18 decks)

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