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Life Protection > Week 16 - Multiple Myeloma > Flashcards

Week 16 - Multiple Myeloma Flashcards

1
Q

What are antibodies?

A

Immunoglobulins / gammaglobulins that are produced to respond to foreign structures (antigens)

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2
Q

What part of the antigen is recognised by the antibody?

A

Epitope

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3
Q

Broad role of T lymphocytes and B lymphocytes

A

T - cellular immunity B - humoral (serum) immunity

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4
Q

What is the main function of antibodies?

A

to neutralise and eliminate the Ags they recognise

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5
Q

What are the two forms of antibodies?

A

membrane bound on B cell surface Secreted (circulation, tissues, mucosa)

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6
Q

Describe activity of membrane bound Igs

A

On B cell surface, generally IgD and IgM I don’t think membrane bound antibodies have significant effector functions

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7
Q

Describe activity of secreted Igs

A

Circulate in blood, can access sites of pathogens Binding abilities AND effector functions May float around as monomer (IgG, IgA, IgE) dimer (IgA) or pentamer (IgM)

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8
Q

Structure of antibodies

A

two identical heavy chains + two identical light chains 5 types of heavy chains , 2 types of light chains

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9
Q

Main components of serum antibody concentrantion

A

IgG (5-16g/L); IgA (0.8-4g/L); IgM (0.5-2g/L)

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10
Q

What might you find in urine?

A

Light chain small enough to get into urine, useful diagnostic feature for some cancers if found in urine

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11
Q

Which immunoglobulin has 4 regions in its heavy chain? How many do the others have?

A

IgM 3

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12
Q

Types of epitopes (2)

A

Linear - adjacent amino acid residues COnformational epitopes - non-sequential

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13
Q

What are the effector functions of antibodies?

A

Neutralisation of microbes, toxins Opsonisation of microbes (marking them for phagocytosis) Activation of complement Antibody-dependent cell-mediated cytotoxicity (marking tumour cells for NK cells to find)

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14
Q

Describe hypervariable regions

A

Portion of antibody that will directly bind with antigen, this bit changes the most to make sure as many antigens as possible can be caught

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15
Q

Generally describe principles of generation of antibody diversity

A

During development - antibody genes are rearranged to make various alternatives (recombine using VDJ regions)

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16
Q

What is allelic exclusion?

A

One (heavy chain or light chain segment) is made first - if okay, the other one is made for the set

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17
Q

What is clonal selection?

A

Antibodies are waiting in the lymph tissues/organs - when an antigen shows up, the correct clone is multiplied to deal with it

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18
Q

Which classes of antibodies work best at different sites and against certain pathogen (blood, mucosa, parasites)

A

Blood - IgG, IgM Mucosa - IgA Parasites - IgE

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19
Q

Describe the principles of antibody isotype switching

A

xxx SLIDE 46 Variable region does NOT change Why would it switch? To preform different effector functions

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20
Q

What prompts B cells to start isotype switching?

A

T helper cells

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21
Q

Describe purpose / role of polymeric (pentameric IgM

A

Stronger and can bind to more antigens (10 sites)

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22
Q

What is the only antibody that can cross the plcenta to provide neonatal protection?

A

IgG

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23
Q

What is the main type of antibody in mucosal secretions? And where?

A

AgA - survives longer as dimer GI , resp, breast milk

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24
Q

Roles of IgE

A

Fighting parasites, allergic reactions (type 1 hypersensitivity such as asthma)

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25
Q

If you detect IgM what does it mean?

A

Early infection (first one to be produced)

26
Q

What is myeloma?

A

Malignant tumour arising in bone marrow Monoclonal plasma cells

27
Q

What is a plasma cell?

A

B-lymphocytes that release antibodies in response to antigens

28
Q

How is myeloma diagnosed by pathologists?

A

Infiltration of bone marrow by abnormal number of plasma cells (more than 30%) Alongside other clinical evidence

29
Q

How can you identify plasma cells (histopathology)?

A

‘Eccentric’ nucleus, with pale blob next to it

30
Q

Describe kappa vs lambda staining

A

Identifying the light chains Using light stain restriction If the ratio is much different, you know if it is neoplastic condition rather than inflammation

31
Q

Diagnostic criteria for plasma cell myeloma

A

Marrow plasmacytosis >30% Plasmacytoma on biopsy M-component - serum (IgG>3.5; IgA>A>2) and urine (1g/24hr of Bence Jones Protein) + minor criteria Lytic bone lesions Reduced normal immunoglobulins Major criteria but to lesser extent

32
Q

How does plasma cell myeloma affect the body? (4)

A

Tumour eroding bone Replacement of the bone marrow (which results in anaemia, other issues) Kidney - build up of light chain which damages tubules Tissues - amyloid build up

33
Q

Role of osteoblasts vs osteoclasts

A

Osteoblasts - make bone Osteoclasts - break bone down Cytokines disrupt the relationship between these components

34
Q

What does the breakdown of bone result in?

A

Calcium released into the blood

35
Q

Components of renal failure in myeloma

A

Free light chain form solid casts in nephron The free light chain can also form amyloid which can cause proteinuria and nephrotic syndrome Effects of hypercalcaemia (causes dehydration) Effects of NSAIDs taken for bony pain

36
Q

What is amyloid? Why do they appear and what do they cause?

A

Amyloid is a collection of any protein which has assembled abnormally into B-pleated sheets. They become insoluble and build up in extracellular spaces leading to cell strangulation and death

37
Q

What are the types of amyloid?

A

AL - Immunoglobulin light chain AA - Serum amyloid A (caused by chronic inflammation) AB - Amyloid prescursor protein (Alzheimer’s)

38
Q

What is the diagnostic histopathological feature of amyloid?

A

Polarised light makes amyloid glow apple green Congo red stain will also turn it red but this is not diagnostic

39
Q

Histopathological investigations for myeloma (2)

A

Bone marrow biopsy Serum electrophoresis

40
Q

Describe major complications of myeloma (4)

A

Calcium high Renal dysfunction Anaemia Bone lesions (lytic)

41
Q

What is MGUS?

A

Premalignant issue xxxxxxxxx

42
Q

What is the progression through different stages of myeloma?

A

Premalignant MGUS Smouldering (asymptomatic) myeloma Symptomatic myeloma Relapsed and refractory myeloma Plasma cell leukaemia

43
Q

What is a plasma cell?

A

Terminally differentiated B lymphoid cell

44
Q

Most common types of antibody in myeloma (3)

A

IgG (60%) IgA (20-25%) Light chains only (15-20%) BUT 5% are non-secretory (can’t pick up anything in blood tests)

45
Q

What tests are required to diagnose myeloma?

A

Hint there is something wrong - anaemia (so Hb), raised ESR Test - FBC, blood chemistry, electrophoresis, BM aspirate, Imaging (e-ray, CT, MRI, PET), genetic profiling

46
Q

Diagnostic differences between MGUS, smoldering, and multiple myeloma

A

More or less than 10% plasma cells - between MGUS and myeloma end organ damage - between smoldering and multiple

47
Q

Defining high risk smoldering and management

A

High risk smouldering myeloma with 70-80% chance of disease progression in 2 years 3 criteria S- BM >60% clonal plasma cells Li- SFLC ratio >100 M- 2 or more lesions on MRI

48
Q

Outline the pain associated with myeloma (2)

A

Pain as a complication of disease - bone and nerve Pain as a complication of treatment

49
Q

Outline imaging recommendations for patients with myeloma

A

Whole-body MRI scanning is first-line (BUT not often and option) Whole body low dose CT is next best Next option is skeletal survey (but plain x-rays not very sensitive)

50
Q

What % of patients with myeloma have bone pain?

A

75%

51
Q

Components of good history for bone pain

A

Quality of the pain Site of the pain Associated symptoms

52
Q

Why do patients with multiple myeloma get pain?

A

Tumour volume Lytic lesions Pathological fractures Nerve root or spinal cord compression

53
Q

Outline role of cytokines in myeloma pain

A

Cancer cells release cytokines sensitizing neurones. This can lead to up regulation of pain receptors, central sensitization in spinal cord and long-term potentiation

54
Q

Outline the role of RANKL

A

Rank ligand inhibitors work directly to regulate osteoclasts - but not more effective than bisphosphonates so far and much more expensive

55
Q

Treatment goals with multiple myeloma (5)

A

Induce remission, if possible Prevent immune suppression Prevent hematologic abnormalities (anemia, low platelets) Prevent end-organ damage Prevent fractures Maintain function, quality of life, control symptoms

56
Q

Potential treatments for pain

A

Gabapentin, opiates / fentanyl, benzodiazepines

57
Q

Treatment options for myeloma

A

PICTURE

58
Q

Potential surgical interventions in myeloma (5)

A

Stabilising fractures Decompression of spinal cord Vertebroplasty Balloon kyphoplasty Radiotherapy

59
Q

Role of bisphosphonates and how they work? What is a significant risk?

A

Role in treatment of malignant hypercalcaemia and bone pain Inhibitors of osteoclastic bone resorption Reduction in vertebral and non vertebral fractures in MRC myeloma VI trial Can contain nitrogen or not, they have high affinity to bone and then are ingested by osteoclsts BUT RISK OF significant jaw damage

60
Q

Describe the relationship between myeloma and peripheral neuropathy - what factors make it more likely?

A

Can be disease related (amyloid, nerve root compression, etc.) or co-morbidities (diabetes / weight loss) or drug related (thalidomide / preosome inhibitors etc) Can cause sensory, motor or autonomic symptoms

61
Q

What scale of patients with myeloma have peripheral neuropathy?

A

11-20% of newly diagnosed patients 83% in relapsed / refractory patients

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