myeloma and other dyscrasia

Question 1

what is the function of B cells

Answer 1

antibody production

acting as antigen presenting cells

Question 2

what are immunoglobulins

Answer 2

antibodies produced by B-cells and plasma cells

Question 3

what are immunoglobulins made up of

Answer 3

proteins
2 heavy chains (u, alpha, delta, gamma, epsilon)
2 lights chains (K or lambda)

Question 4

which immunoglobulins are monomeric

Answer 4

IgD
IgE
IgG

Question 5

which immunoglobulins are dimeric

Answer 5

IgA

Question 6

which immunoglobulins are pentameric

Answer 6

IgM

Question 7

where does initial production and development of B cells occur

Answer 7

in the bone marrow

Question 8

at what stage of development are B cells when they leave the marrow

Answer 8

immature B cells with Ig on their surface

Question 9

what do B cells do in the periphery

Answer 9

travel to the follicle germinal centre of the lymph node

identify antigen and improve fit by somatic mutation or deletion

may return to marrow as plasma cell or circulate as memory cell

Question 10

what do plasma cells do

Answer 10

produce lots of antibodies

Question 11

what are features of plasma cells

Answer 11

eccentric ‘clock face’ nucleus
open chromatin
plentiful blue cytoplasm
pale perinuclear area

Question 12

what is the difference between polyclonal and monoclonal

Answer 12

polyclonal cells/antibodies come from many different parent cells

monoclonal cells/antibodies all come from a single precursor

Question 13

what might cause a polyclonal increase in immunoglobulins

Answer 13

infection
autoimmune conditions
malignancy (reaction of the host to malignant clone)
liver disease

Question 14

what is another word for monoclonal immunoglobulin

Answer 14

paraprotein

Question 15

what are monoclonal immunoglobulins a marker of

Answer 15

underlying clonal B-cell disorder

Question 16

how are immunoglobulins detected/analysed

Answer 16

serum electrophoresis

Question 17

what is the purpose of serum immunofixation

Answer 17

to classify the abnormal protein band

Question 18

what are bence jones proteins

Answer 18

immunoglobulin light chains present in urine

Question 19

how are bence jones proteins detected

Answer 19

urine electrophoresis

Question 20

are free light chains pathological?

Answer 20

free light chain production of 0.5 g/day is normal

Question 21

why is there physiological free light chain production

Answer 21

plasma cells produce more light chains than heavy chains so free light chains get secreted into the plasma

Question 22

are free light chains monomeric or dimeric

Answer 22

kappa light chains are monomeric

lambda light chains are dimeric

Question 23

what are causes of paraproteinaemia (monoclonal antibodies)

Answer 23

MGUS (asymptomatic)
myeloma 
amyloidosis
lymphoma
chronic lymphocytic leukaemia

Question 24

what is myeloma

Answer 24

a plasma cell malignancy

Question 25

what are direct tumour cell effects of myeloma

Answer 25

bone lesions increased calcium bone pain marrow failure due to replacement of normal marrow

Question 26

what are paraprotein mediated effects of myeloma

Answer 26

renal failure immunosuppresion hyperviscosity amyloid

Question 27

what is the most common type of myeloma

Answer 27

IgG | followed by IgA, then bence jones myeloma

Question 28

how does myeloma cause lytic bone disease

Answer 28

myeloma cells secrete IL-6 which causes osteoblast suppression and osteoclast activation (also releases calcium)

Question 29

what are symptoms of hypercalcaemia

Answer 29

stone, bones, abdominal groans and psychiatric moans | thirst, dehydration and renal impairment

Question 30

how does myeloma cause renal failure

Answer 30

tubular cell damage by light chains light chain deposition causes cast nephropathy sepsis, hypercalcaemia, dehydration, drugs

Question 31

in which part of the nephron does cast nephropathy occur

Answer 31

thick ascending limb of loop of Henle

Question 32

how does cast nephropathy occur

Answer 32

light chains react with proteins produced in the thick limb of loop of henle to produce insoluble casts that block the nephron

Question 33

how can cast nephropathy potentially be reversed

Answer 33

hydration stop nephrotoxic drugs steroids/chemo to prevent light chain production

Question 34

how is myeloma managed

Answer 34

combination chemotherapy is the mainstay | steroids, alkylating agents, new agents

Question 35

examples of alkylating agents

Answer 35

cyclophosphamide | melphalan

Question 36

examples of new chemotherapy agents used in myeloma treatment

Answer 36

thalidomide bortezomib lenalidomide

Question 37

which myeloma treatment is suitable for fit patients

Answer 37

high dose chemo and autologous stem cell transplant

Question 38

what is used to monitor response to myeloma treatment

Answer 38

paraprotein level

Question 39

what are the steps involved in autologous haematopoietic stem cell transfer

Answer 39

administer pre-treatment to release blood stem cells from bone marrow into blood stream collect stem cells and freeze until needed administer chemo to remove/partially remove immune system return stem cells by infusion into vein provide supportive treatment until immune system rebuilds

Question 40

how are symptoms controlled in myeloma

Answer 40

opiate analgesia local radiotherapy (pain relief/spinal cord compression) bisphosphonates (correct hypercalcaemia and bone pain) vertebroplasty (sterile cement to stabilised fractured bone)

Question 41

what is MGUS

Answer 41

monoclonal gammopathy of undetermined significance

Question 42

how is MGUS defined

Answer 42

paraprotein <30 g/l bone marrow plasma cells <10% no evidence of myeloma end organ damage

Question 43

what causes AL amyloidosis

Answer 43

mutation in light chain causing altered structure | results in precipitates forming in tissues as an insoluble beta pleated sheet

Question 44

how is AL amyloidsis treated

Answer 44

chemo to switch of light chain supply

Question 45

which organs can be damaged in AL amyloid

Answer 45

kidney: nephrotic syndrome heart: cardiomyopathy liver: organomegaly and deranged LFTs neuropathy: autonomic/peripheral GI tract: malabsorption

Question 46

how is amyloid diagnosed

Answer 46

congo red stain on organ biopsy (rectal or fat biopsy is less invasive) evidence of deposition in other organs SAP scan echo/cardiac MRI nephrotic range proteinuria

Question 47

what does a SAP scan do

Answer 47

radio-labelled serum amyloid P localises rapidly and specifically to amyloid deposits in proportion to the quantity of amyloid present

Question 48

what are SAP scan used for

Answer 48

monitor disease burden and treatment response

Question 49

what is the buzzword for amyloid in Congo red staining

Answer 49

'apple-green' birefringence under polarised light

Question 50

what cells are affected in Waldenstrom's macroglobulinaemia

Answer 50

clonal disorder of cells intermediate between a lymphocyte and a plasma cell

Question 51

which Ig is produced in Waldenstrom's macroglobulinaemia

Answer 51

IgM | pentameric = large = macroglobulin

Question 52

what are clinical features of waldenstrom's

Answer 52

hyper viscosity syndrome: fatigue, visual disturbance, confusion, coma, bleeding, cardiac failure night sweats weight loss

Question 53

how is waldenstrom's treated

Answer 53

``` chemo plasmapheresis (removes paraprotein from the circulation) ```