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Haematology > Myeloma > Flashcards

Myeloma Flashcards

1
Q

Where are B cell derieved from

A

Pluripotent haematopoietic stem cells.

Lymphoid lineage.

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2
Q

What is the role of B cells?

A

Part of adaptive immune response.
Antibody production = main role.
Also act as antigen presenting cells.

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3
Q

What are immunoglobulins?

A

Antibodies produced by B cells and plasma proteins.

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4
Q

what makes up immunoglobulins

A

Proteins made up of 2 heavy chains and 2 light chains (kappa or gamma)

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5
Q

what immunoglobulins are monomers

A

IgD, Ige, IgG

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6
Q

What immunoglobulins are dimers

A

IgA

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7
Q

What immunoglobulin is a pentamer

A

IgM

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8
Q

Where do B cells move to in the periphery

A

the follicle germinal centre of the lymph node (lymphoid follicle)

Identifies the antigen and improves the fit by somatic mutation or be deleted.

May return to the marrow as plasma cell or circulate as memory cell.

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9
Q

Why type of B cell gives rise to all the other B cell types.

A

IgM

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10
Q

What are the morphological features of a plasma cell?

A

‘Clock face nucleus’
Open chromatin - synthesising mRNA
Plentiful blue cytoplasm- laden with protein
pale perinuclear area - Golgi apparatus

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11
Q

What is meant by a polyclonal increase in Ig

A

Ig produced by many different plasma cell clones.

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12
Q

When does polyclonal Ig increase occur

A

Infection
Autoimmune
Malignancy
Liver disease

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13
Q

What is a monoclonal rise in Ig

A

All Ig derived from clonal expansion of a single B-cell

Identical antibody structure and specificity

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14
Q

What is a paraprotein

A

A monoclonal immunoglobulin

= marker of underlying clonal B- cell disorder

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15
Q

Which protein is closest to the anode in electrophoresis

A

Albumin - it is the most negatively charged

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16
Q

What is contained in the alpha 1 band

A

alpha 1 antitrypsin

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17
Q

What is contained in the alpha 2 band

A

alpha macroglobin, caeruloplasmin, haptoglobin

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18
Q

what is in the beta band

A

transferrin, low density lipoprotein, C3

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19
Q

What is in the gamma band

A

Immuniglobulins

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20
Q

What does serum electrophoresis achieve

A

detects abnormal protein bands

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21
Q

What does serum immunofixation do?

A

classify the abnormal protein band ie to find which paraprotein it is

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22
Q

What is Bence - jones protein

A

When Ig are synthesised in plasma cells - more light chains than heavy chains are produced and some of the light chains leack into the plasma. If there is an increase in polyclonal (infection) or monoclonal (myeloma) plasma cells then the amount of free light chains will increase. Excess can leak into the urine as BJP

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23
Q

What is a normal level of BJP

24
Q

Which light chains are usually monomers

25
which light chains are usually dimers
lambda
26
What are the three most common causes of paraproteinaemia
MGUS Myeloma Amyloidosis
27
What are the other less common causes of paraproteinaemia
``` Lymphoma Asymptomatic myeloma Solitary/extramedullary plasmacytoma Chronic lymphocytic leukaemia Waldenstroms macroglobulinaemia ```
28
What is myeloma
It is a malignancy of the plasma cells. | In which monoclonal malignant plasma cells produce paraproteins.
29
What effects do the tumour cells have on the body in myeloma?
Bone lesions - lytic Increase calcium Bone pain Replace bone marrow --> marrow failure
30
What effects do the paraproteins in myeloma have on the body
renal failure immune suppression hyperviscosity amyloid
31
What is the most common tupe of monoclonal protein produced in myeloma in the UK
IgG
32
What type of bone disease occurs in myeloma
osteolytic
33
Why does lytic bone disease occur in myeloma.
There is activation of osteoclasts and suppression of osteoblasts.
34
What occurs due to increase in osteoclast activity
Increased calcium
35
what causes the suppression of osteoblasts and activation of osteoclasts
IL 6
36
What are the symptoms of hypercalcaemia
``` Stones- biliary or hepatic Bone pain Abdominal pain/ nausea and vomiting Psychiatric moan Thirst Polyuria - dehydration renal impairment psychiatric symptoms ```
37
What percentage of myeloma patients have renal impairement at diagnosis?
30 percent
38
Why does myeloma cause renal impairment
``` Tubular cell damage by light chains Light chain deposition = cast nephropathy Sepsis Hypercalcaemia and dehydration NSAIDS Amyloid Hyperuricaemia ```
39
Is cast nephropathy reversible?
It can be with prompt treatment with steroids/chemo (because this switches off light chain production)
40
What is the median age at diagnosis of myeloma
65
41
What is the mean survival time with myeloma
5-8 years for younger patients with more effective therapy
42
what are the treatments of myeloma?
Corticosteroids = dexamethasone or prednisolone Alkylating agents= mephalan, cycophphamide Novel agents = thalidomide, bortezomib and lenalidomide High dose chemo/autologous tem cell transplant in fit patients
43
How is myeloma response to treatment monitored
Paraprotein levels
44
How are symptoms controlled in myeloma
Opiate analgesia (avoid NSAIDs) Local radiotherapy - pain relief and spinal cord compression Bisphosphonates - hypercalcaemia and bone pain Vertebroplasty - inject sterile cement into fractured bone to stabilise
45
What is MGUS
Monoclonal gammopathy of uncertain significance
46
what is the definition of MGUS
Paraprotien levels less than 30g/l Bone marrow plasma cells less than 10 percent No evidence of myeloma or end organ damage (ie normal calcium, normal renal function, normal Hb, no lytic lesions, no increase in infections)
47
In what age group os MGUS most common
elderly Increasing incidence with age 15 percent in those over 90 yrs twice as common in black people
48
what is the risk of progression from MGUS to myeloma
1 percent per year
49
What is AL Amyloidosis
A rare multisystem, slowly progressive disorder in which there is mutation in the light chains resulting in altered structure and amyloid depositions in various organs as insoluble beta pleated sheets.
50
What organs can be damages in AL amyloidosis
``` kidney - nephrotic syndrome Heart - cardiomyopathy - poor prognosis Liver Neuropathy- autonomic, peripheral GI tract- malabsoption ```
51
How is a diagnosis of AL amyloidosis made
Organ biopsy confirming AL amyloid deposition - congo red stain - rectal or fat biopsy can be done if high clinical suspicion as it is less invasive evidence of deposition in other organs eg sAP scan, echo, proteinuria
52
What is the appearance of AL amyloidosis under polarised light
Apple green birefringence
53
What is waldenstroms macroglobulinaemia
It is a lymphoplasmacytois neoplasm meaning it is a disorder of cell intermediates between a lymphocyte and a plasma cell.
54
What paraprotein is characteristic of waldenstorms
IgM
55
What are the clinical features of waldenstroms
Hyperviscosity syndrome - fatigue, bleeding, cardiac failure, visual disturbance, confusion, coma B symtoms- night sweats, weight loss
56
How is WM treated
chemo | plasmpaheresis (removes paraprotein from the circulation)

Haematology (21 decks)

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