Myeloma and Paraproteins

Question 1

what test is doen for possible myeloma?

Answer 1

serum electrophoresis

Question 2

what is true about MGUS

Answer 2

50% have lytic bone disease, anaemia, hypercalcaermia or renal failure

Question 3

what are the different types of heavy chains?

Answer 3

Gamma – IgG
Alpha – IgA
Mu – IgM
Delta – IgD
Epsilon - IgE

Question 4

what is the function of each heavy chain

Answer 4

IgM - Initial phase of antibody production, Exists as a pentamer – highest molecular weight
IgG - Most prevalent antibody subclass (75% of total)
IgA - Mucous membrane immunity
IgE - Parasite immune responses, hypersensitivity

Question 5

what is the fab and fc region?

Answer 5

fab - variable, defines target binding. Fc - constant, defined by heavy chains

Question 6

what is a paraprotein and what does it tell us?

Answer 6

unique monocloncal population present in the blood or urine, if it is present it tells us that there is a monocloncal proliferation of a B lymphocyte/plasma cell somewhere in the body.

Question 7

outline the process of serum electrophoresis

Answer 7

seperates protein based on its size and charge, Forms a characteristic pattern of bands of different widths and intensities based on proteins present

Question 8

what does electropheoresis assess

Answer 8

antibody diversity, identifies Paraprotein

Question 9

what does immunmofixation assess?

Answer 9

Identifies what class of paraprotein is present (i.e. IgG, IgM)

Question 10

what does a IgM paraprotein indicate?

Answer 10

Lymphoma - mature b cell

Question 11

what does IgG, IgA paraproteins indicate?

Answer 11

myeloma - mature plasma cells

Question 12

what is MGUS (monoclonal gammopathy of unknown significance)

Answer 12

a monocloncal paraprotien without other features of myeloma

Question 13

what is MYELOMA

Answer 13

Neoplastic disorder of plasma cells, resulting (usually) in excessive production of a single type of immunoglobulin (paraprotein) (a clone of cancerous plasma cells which fill the bone marrow and produce only a single immunoglobulin type)
Peaks in 7th decade
Ethnicity – commoner in black population than white
Clinical manifestations may result from direct effect of plasma cells, or effect of paraprotein

Question 14

what what are the CRAB features?

Answer 14

CRAB – hyperCalcaemia, Renal failure, Anaemia, Bone disease

Question 15

how may anaemia form in there patients?

Answer 15

tumour infiltration - renal impairment - cytokine mediated anaemia

Question 16

explain how bone is effected?

Answer 16

osteoclasts stimulated by myeloma cytokines, also hypercalcaemia is caused by excess calcium is released into blood from bone.

Question 17

explain why patients may present with confusion

Answer 17

hyperviscocity, hypercalcaemia, infection.

Question 18

what are the other features of myeloma?

Answer 18

bone disease
lytic bone lesions
pathological fractures
cord compression
hypercalcaemia
bone marrow failure esp. anaemia
Infections

Question 19

why are the kidneys commonly effected in myeloma?

Answer 19

excess of light chains produced (Bence jojnes proteins) these proteins are deposited in the kidney interfereing with its function.

Question 20

what are the effects of the paraprotein?

Answer 20

Renal failure – cast nephropathy: Immunoglobulin deposition and blockage of renal tubules.
Hyperviscosity - Syndrome caused by increased viscosity in blood, impaired microcirculation and hypoperfusion. Commonest clinical feature is bleeding – retinal, oral, nasal, cutaneous. Can also cause cardiac failure, pulmonary congestion, confusion, renal failure.
Hypogammaglobulinaemia - Impaired production of normal Immunoglobulin. Tendency to infection.

Question 21

define amyloidosis…

Answer 21

Amyloidosis
Group of diseases characterised by deposition of fibrillar protein
Morphological appearances, physical structure are similar
Biochemical or protein composition can vary.
(crystalline protein structure)

Question 22

what can amyloidosis cause?

Answer 22

Nephrotic syndrome
Cardiac failure (LVH)
Carpal tunnel syndrome
Autonomic neuropathy
Cutaneous infiltration

Question 23

Dx of myeloma?

Answer 23

Myeloma is diagnosed by finding excess plasma cells in the bone marrow - pye: IgG, IgA and light chain
Must comprise > 20% of total bone marrow cell population
on cxr skull has a perrper pot appearance, fbc - low hb, uande - high creatinine, serum electrophoresis - monoclonal immunoglobulins.

Question 24

how common are paraproteins?

Answer 24

Paraproteins are common
3-4% of population over age of 75
The vast majority have nothing wrong with them
This is termed monoclonal gammopathy of uncertain significance (MGUS)

Question 25

Myeloma Tx

Answer 25

Chemotherapy - Proteasome inhibitors (carfilzomib, bortezomib), IMiDs (lenalidomide, pomalidomide), monoclonal antibodies
Bisphosphonate therapy - Zoledronic acid
Radiotherapy
Steroids
Surgery
Pinning of long bones; decompression of spinal cord
Autologous stem cell transplant

Question 26

does igm myelome exist?

Answer 26

No

Question 27

how do igm paraproteins present?

Answer 27

IgM paraproteins are associated with low-grade lymphomas (various types)
Clinical presentation - Bone marrow failure (anaemia, thrombocytopenia), Lymphadenopathy, Hepatosplenomegaly, B symptoms.