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Haematology Year 3 > Myeloma + Other Plasma Cell Disorders > Flashcards

Myeloma + Other Plasma Cell Disorders Flashcards

1
Q

where are B cells derived from

A

pluripotent haematopoietic stem cells in the bone marrow

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2
Q

role of B cells

A

part of adaptive immune system

  • antibody production
  • act as antigen presenting cells
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3
Q

what are immunoglobulins

A

antibodies produced by B cells and plasma cells

proteins made up 2 heavy and 2 light chains

each antibody recognises a specific antigen

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4
Q

what immunoglobulins are monomer shaped

A

IgG
IgD
IgE

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5
Q

what immunoglobulins are dimer shaped

A

IgA

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6
Q

what immunoglobulins are pentamer shaped

A

IgM

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7
Q

normal pathway of lymphocyte maturation

A

stem cells – lymphoid progenitors – pro B cells – pre B cells – IgM B cells

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8
Q

what do IgM B cells divide to make

A

IgM plasma cells
IgA
IgE
IgG

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9
Q

what does IgG eventually go on to become

A

plasma cells

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10
Q

function of plasma cell

A

to produce large quantities of antibodies when needed

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11
Q

how does the nucleus appear in a plasma cell

A

clock face nucleus

- nucleus off to one side

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12
Q

role of B cells in the periphery

A

travel to follicle germinal centre of the lymph node
identify the antigen
may return to the marrow as a plasma cell or circulate as a memory cell

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13
Q

what is meant if a blood film is described as

  • polyclonal
  • monoclonal
A

polyclonal = multiple types of blood cells, can be seen as a part of normal function

monoclonal = one type of cell seen, suggests pathology

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14
Q

what are the causes of polyclonal increase in immunoglobulins

A

infection
autoimmune
malignancy
liver disease

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15
Q

what does a monoclonal increase in immunoglobulins imply

A

implies that the antibody is all identical + produced by a single B cell

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16
Q

what can monoclonal immunoglobulins also be called

A

paraprotein

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17
Q

what are paraproteins a marker of

A

underlying clonal B cell disorder

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18
Q

how can you detect immunoglobulins

A

serum electrophoresis

- separated serum proteins appear as distinct bands/zones

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19
Q

what zone are immunoglobulins seen in on electrophoresis

A

gamma

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20
Q

what is bence-jones protein

A

excess immunoglobulin light chains leaking into the urine
– paraproteinaemia

detected by urine electrophoresis

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21
Q

what happens to amount of free light chains in the plasma when a person is unwell (i.e. infection/monocloncal disease)

A

increase in free light chains in the plasma

22
Q

causes of paraproteinaemia

A

monoclonal gammopathy of undetermined significance (MGUS- completely harmless)
myeloma
amyloidosis
lymphoma

23
Q

what is a myeloma

A

plasma cell malignancy - clonal proliferation of plasma cells resulting in increased monoclonal antibody (usually IgG or IgA)

24
Q

direct tumour effects of a myeloma

A

bone lesions - lytic lesions
increased calcium
bone pain/ pathological fractures
bone marrow failure - anaemia, bleeding, infections

25
Q

effects of paraprotein seen in myeloma

A

renal failure
immunosuppression
hyperviscosity
amyloid

26
Q

how is myeloma classified

A

by type of antibody produced

27
Q

most common myeloma

A

IgG

28
Q

types of myeloma from most to least common

A
  • IgG
  • IgA
  • Bence Jones
  • non secretory
  • IgD
  • biclonal
  • IgE
29
Q

what is a myelomas affect on bone

A

lytic bone disease

clones produce IL-6 which activates osteoclasts and inhibits osteoblasts – bone destruction

30
Q

what is seen on x ray of myeloma

A

“punched out” lytic lesions

pepper pot skull

31
Q

symptoms of hypercalcaemia

A 
stones
bones 
abdominal groans
psychiatric moans
thirst/dehydration
renal impairement
32
Q

how can a myeloma cause kidney failure

A

free light chains accumulate in the proximal tubules before entering loop of henle

combine with Tamm-horsfall protein to produce insoluble casts blocking the nephron – cast nephropathy

this leads to renal failure

33
Q

where in the loop of henle is Tamm-Horsfall protein produced

A

thick ascending limb

34
Q

what is the significance of Tamm-Horsfall protein in renal failure

A

free light chains bind with the protein causing insoluble casts that block the nephron

this causes cast nephropahty resulting in renal failure

35
Q

mean age of myeloma diagnosis

A

65

36
Q

treatment of myeloma

A

bone pain – analgesia + biphosphonates

anaemia – transfusions/ EPO

hypercalcaemia – adequate hydration

hyper viscosity – plasmapheresis

chemo: melphalan + prednisone + lenalidomide

young patients may receive allogenic bone marrow transplant

37
Q

how is response to treatment monitored

A

paraprotein level

38
Q

symptom control in myeloma

A
  • opiate analgesia
  • local radiotherapy - good pain relief for spinal cord compression
  • biphosphonates - correct hypercalcaemia + bone pain
  • vertebroplasty - infection of sterile cement into fractured bone to stabilise it
39
Q

what does MGUS stand for

A

monoclonal gammopathy of uncertain significance

40
Q

definition of MGUS

A 
paraprotein < 30 g/l
bone marrow plasma cells <10%
no evidence of myeloma end organ damage :
- normal calcium
- normal renal function
- normal Hb
- no lytic lesions
41
Q

what is amyloidosis

A

accumulation of protein in abnormal fibrillar form
- precipitates in tissues as an insoluble beta pleated sheet
caused by mutations in the light chain – causes organ damage

42
Q

what can amyloidosis cause

A

nephrotic syndrome

cardiomyopthay

43
Q

how is amyloidosis deposition confirmed

A

congo red staining - causes apple green birefringence under polarised light

44
Q

what is waldenstrom macroglobulinaemia

A

lymphoplasmacytoid neoplasm

  • clonal disorder of cells intermediate between a lymphocyte and a plasma cell
  • characteristic IgM paraprotein
45
Q

what is characteristic of waldenstroms macroglobulinaemia

A

IgM paraprotein

46
Q

tumour effects of waldenstroms macroglobulinaemia

A

lymphadenopathy
splenomegaly
marrow failure

47
Q

IgM paraprotein effects in waldenstroms macroglobulinaemia

A

hyper viscosity

neuropathy

48
Q

features of hyper viscosity

A 
fatigue 
visual disturbance
confusion
bleeding
cardiac failure
night sweats
weight loss
49
Q

treatment of waldenstroms macroglobulinaemia

A 
chemotherapy 
plasmapheresis (removes paraprotein from circulation)
50
Q

effects of zolendronate in myeloma

A

this is a biphosphonate that inhibits osteoclast activity so halts the progression of bone disease

51
Q

what drug regime is used in relapsed myeloma

A

lenalidomide + bortezomib (protesome inhibitor)

52
Q

blood results in myeloma

A

anaemia, thrombocytopenia, leucopenia

increased calcium, increased urea, increased creatinine, increased ESR

Haematology Year 3 (21 decks)

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