12.3 Multiple Myeloma

Question 1

Outline the basic structure of antibodies

Answer 1

• Heavy chain (base of Y)
• Light chain (form part of tips of Y)
• Variable region (outermost part; unique to each clone)

Question 2

What is the role of B cells and plasma cells in antibody generation?

Answer 2

• B cells mature into plasma cells
• Plasma cells produce signature antibodies

Question 3

What are the different kinds of antibodies

Answer 3

GAMED

Question 4

What is Monoclonal gammopathy of unknown significance (MGUS)?

Answer 4

Asymptomatic paraproteinaemia

Question 5

How can MGUS progress to multiple myeloma?

Answer 5

• Genetic mutations in altered plasma cells (such as immune evasion)
• • changes changes to bone marrow microenvironment
• Angiogenesis
• This all supports the crowding out of bone marrow by altered plasma cells

Question 6

Multiple myeloma clinical features + why they occur

Answer 6

• Punched out lesions (interrupted blast-clast balance, in favour of clasts)
• Hypercalcaemia (bone lysis)
• Kidney injury (light chain nephropathy, causes Bence Jones proteins)
• Bone marrow plasmacytosis (duh)
• Anaemia, pancytopaenia, thrombocytopaenia, raised ESR [chronic] (other cells crowded out)
• Easy bruising (thrombocytopaenia)

Question 7

Epidemiology of multiple myeloma (demographics, risk factors)

Answer 7

• More common in older males
• RFs: FHx, obesity, other plasma cell diseases like MGUS

Question 8

How can multiple myeloma cause AKI?

Answer 8

• Altered plasma cells pump out huge volumes of light chains, + cross GBM
• These soon saturate renal resorption mechanisms, forming casts in the tubules
• This blockage from casts cause interstitial inflammation and prevents kidney function (can also cause irreversible fibrosis)

Question 9

Outline the broad treatment principles of multiple myeloma

Answer 9

1. Treat primarily w/ chemotherapy
2. Correct hypercalcaemia if acutely worrisome
3. Urine alkalination may slow cast formation if indicated
4. Dialysis may be required in renal failure

(So: chemo + correct calcium + renal)

Question 10

How can serum biochemistry look in multiple myeloma?

Answer 10

• Hyperglobulinaemia (duh)
• Hypercalcaemia (why?)
• AKI indications (high creatinine, low GFR)

Question 11

List 5 diagnostic tests for multiple myeloma

Answer 11

• Detection of serum paraprotein
• Detection of serum light chain
• Urinary Bence Jones protein
• Bone marrow biopsy
• Radiology (punched out lesions)