Multiple Myeloma Flashcards
what is multiple myeloma?
cancer of the PLASMA cells in the bone marrow.
plasma cells are a type of B lymphocytes which produce antibodies. you get large quantities of a single type of antibodies being produced
multiple myeloma
myeloma affects multiple areas of the body
MGUS- Monoclonal gammopathy of undetermined significance
excess of a single type of antibody or antibody components without features of myeloma or cancer
incidental finding
significance is unclear
follow up for monitor of progression of the disease.
smouldering myeloma
progression of MGUS with higher levels of antibodies or antibody components.
premalignant and more likely to progress to myeloma than MGUS
Waldenstrom’s macroglobulinaemia is a type of smouldering myeloma where there is excessive IgM
what is the pathophysiology of myeloma?
plasma cells (b cells) (b lymphocytes) are activated to produce a certain antibody. if there is a genetic mutation, then a specific type of plasma cell rapidly and uncontrollably multiplies
plasma cells produce ONE type of antibody (immunoglobulins)
immunoglobulins
aka antibodies complex molecule two heavy chains two light chains Y shaped
help the immune system to recognise and fight infection
5 main types A, G, M, D, E
in myeloma, one of these will be in abundance. most is IgG.
Bence Jones protein
this can be found in urine of many patients with myeloma. actually a part (subunit) of the antibody called the light chain
myeloma bone disease
as a result of increased osteoclast activity and supressed osteoblast activity you can develop myeloma bone disease
osteoclast= absorb bone (break it down, C=cut)
osteoblast= deposit bone (build bone, B) (osteoid and minerals) (ca2+, Po4-)
RANKL binds to RANK on osteoclast which stimulates osteoclastic activity.
osteoblast also release OPG which decreases osteoclastic activity.
metabolism is therefore imbalanced as more is being broken than formed.
this is all due to cytokines released from plasma cells and stromal cells when they are in contact with plasmaa cells
where does myeloma bone disease happen?
the skull, spine, long bones and ribs.
abnormal bone metabolism is patchy -some areas are very thin and some are normal.
‘osteolytic lesions’
weak points can lead to pathological features (vertebral fracture)
hypercalcaemia in myeloma bone disease
hypercalcaemia (high ca2+) as a result of calcium being reabsorbed from the bone into the blood.
plasmacytomas
people with myeloma can develop plasmacytomas. these are individual tumours made up of cancerous plasma cells. can occur in bones and replace normal tisssue
anaemia in myeloma
cancerous plasma cells invade bone marrow (infiltration) which causes a suppression of other blood cells e..g RBC - anaemia, low neutrophils- neutropenia, low platelets- thrombocytopenia.
myeloma of renal disease
Patients with myeloma often develop renal impairment. This is due to a number of factors:
High levels of immunoglobulins (antibodies) can block the flow through the tubules
Hypercalcaemia impairs renal function
Dehydration
Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys
hyper viscocity in myeloma
normal plasma viscosity / internal friction of the flow of blood is between 1.3-1.7 times that of water. (blood is quicker than water)
if there is more protein then there is more plasma viscosity.
this can cause:
Easy bruising
Easy bleeding
Reduced or loss of sight due to vascular disease in the eye
Purple discolouration to the extremities (purplish palmar erythema)
Heart failure
main clinical features of myeloma
(CRAB)
C – Calcium (elevated)
R – Renal failure
A – Anaemia (normocytic, normochromic) from replacement of bone marrow.
B – Bone lesions/pain
- infections
- fractures, dehydration
risk factors: Older age Male Black African ethnicity Family history Obesity
investigations for myeloma
anyone over 60 with persistent bone pain, back pain, unexplained fractures.
FBC (low white blood cell count in myeloma) hypercalcaemia, anaemia, paraprotein reduction of normal anitbiodies Calcium (raised in myeloma) ESR (raised in myeloma) Plasma viscosity (raised in myeloma) serum protein electrophoresis urine Bence-Jones protein test
BLIP B --- Bence–Jones protein (request urine electrophoresis) L – Serum‑free Light‑chain assay I – Serum Immunoglobulins P – Serum Protein electrophoresis
bone marrow biopsy
imaging: MRI, CT, skeletal survey (xray images of full skeleton)
Xray signs of myeloma
Punched out lesions
Lytic lesions
“Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface
management of myeloma
control disease
relapsing-remitting disease
MDT
chemotherapy:
bortezomid
thalidomide
dexamethasone
stem cell transplant VTE prophylaxis (LMWH)
management of myeloma bone disease
bisphosphonate
radiotherapy
orthopaedic surgery
cement augmentation into vertebral fractures or lesions
myeloma complications
Infection Pain Renal failure Anaemia Hypercalcaemia Peripheral neuropathy Spinal cord compression Hyperviscosity
multiple myeloma pathophysiology osteoclastic activity promotion
secrets IL3 by increasing osteoclastic activity.
secrete DKK1 which inhibits OPG by osteoblast (Again most osteoclast activity)
stimulates osteoclast through RANK ligan
light chains are small enough to be filtered by the kidneys- renal failure. urined out- bence-jones protein
