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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

A

0.5g/day

24
Q

Which light chains are usually monomers

A

kappa

25
Q

which light chains are usually dimers

A

lambda

26
Q

What are the three most common causes of paraproteinaemia

A

MGUS
Myeloma
Amyloidosis

27
Q

What are the other less common causes of paraproteinaemia

A 
Lymphoma
Asymptomatic myeloma
Solitary/extramedullary plasmacytoma
Chronic lymphocytic leukaemia
Waldenstroms macroglobulinaemia
28
Q

What is myeloma

A

It is a malignancy of the plasma cells.

In which monoclonal malignant plasma cells produce paraproteins.

29
Q

What effects do the tumour cells have on the body in myeloma?

A

Bone lesions - lytic
Increase calcium
Bone pain
Replace bone marrow –> marrow failure

30
Q

What effects do the paraproteins in myeloma have on the body

A

renal failure
immune suppression
hyperviscosity
amyloid

31
Q

What is the most common tupe of monoclonal protein produced in myeloma in the UK

A

IgG

32
Q

What type of bone disease occurs in myeloma

A

osteolytic

33
Q

Why does lytic bone disease occur in myeloma.

A

There is activation of osteoclasts and suppression of osteoblasts.

34
Q

What occurs due to increase in osteoclast activity

A

Increased calcium

35
Q

what causes the suppression of osteoblasts and activation of osteoclasts

A

IL 6

36
Q

What are the symptoms of hypercalcaemia

A 
Stones- biliary or hepatic
Bone pain
Abdominal pain/ nausea and vomiting
Psychiatric moan 
Thirst 
Polyuria - dehydration
renal impairment
psychiatric symptoms
37
Q

What percentage of myeloma patients have renal impairement at diagnosis?

A

30 percent

38
Q

Why does myeloma cause renal impairment

A 
Tubular cell damage by light chains
Light chain deposition = cast nephropathy
Sepsis
Hypercalcaemia and dehydration
NSAIDS
Amyloid
Hyperuricaemia
39
Q

Is cast nephropathy reversible?

A

It can be with prompt treatment with steroids/chemo (because this switches off light chain production)

40
Q

What is the median age at diagnosis of myeloma

A

65

41
Q

What is the mean survival time with myeloma

A

5-8 years for younger patients with more effective therapy

42
Q

what are the treatments of myeloma?

A

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
Q

How is myeloma response to treatment monitored

A

Paraprotein levels

44
Q

How are symptoms controlled in myeloma

A

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
Q

What is MGUS

A

Monoclonal gammopathy of uncertain significance

46
Q

what is the definition of MGUS

A

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
Q

In what age group os MGUS most common

A

elderly
Increasing incidence with age
15 percent in those over 90 yrs

twice as common in black people

48
Q

what is the risk of progression from MGUS to myeloma

A

1 percent per year

49
Q

What is AL Amyloidosis

A

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
Q

What organs can be damages in AL amyloidosis

A 
kidney - nephrotic syndrome
Heart - cardiomyopathy - poor prognosis
Liver
Neuropathy- autonomic, peripheral
GI tract- malabsoption
51
Q

How is a diagnosis of AL amyloidosis made

A

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
Q

What is the appearance of AL amyloidosis under polarised light

A

Apple green birefringence

53
Q

What is waldenstroms macroglobulinaemia

A

It is a lymphoplasmacytois neoplasm meaning it is a disorder of cell intermediates between a lymphocyte and a plasma cell.

54
Q

What paraprotein is characteristic of waldenstorms

A

IgM

55
Q

What are the clinical features of waldenstroms

A

Hyperviscosity syndrome - fatigue, bleeding, cardiac failure, visual disturbance, confusion, coma

B symtoms- night sweats, weight loss

56
Q

How is WM treated

A

chemo

plasmpaheresis (removes paraprotein from the circulation)

Haematology (21 decks)

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