Narrative of Pathophysiology:

In multiple myeloma, the DNA of plasma cells has been damaged, causing them
to become malignant or cancerous. Instead of forming a lump ortumour, these abnormal
plasma cells, which then become known as myeloma cells, divide and expand within the
bone marrow.Multiple myeloma develops in B lymphocytes after they have left the part
of the lymph node known as the germinal center. The normal cell line most closely
associated with Multiple Myeloma cells is generally taken to be either an activated
memory B cell or the precursor to plasma cells, the plasmablast.Produce adhesive
molecules and bind to Bone Marrow Stromal Cells. Malignant plasmablast grows into
malignant plasma cells. As a result there will be uncontrolled proliferation of malignant
plasma cell clones.
When there is abnormal production of myeloma cells a formation of
plasmacytomas will result. There will be compression of surrounding bone tissue, bone
marrow and nerve endings which can lead to destruction of Bone Cell Marrow. When
there is destruction of bone cell marrow it will decrease osteoblast which is a bone
forming cell and decrease hematopoiesis resulting to low RBC, Megakaryocytes, and
WBC. Leading to Anemia, Thrombocytopenia resulting to bleeding, and leukopenia
resulting to increase susceptibility to any infections.
Another thing that plasmacytoma cause is the release of IL-6 and Tumor
Necrosis Factor which recruits and activates the osteoclast (cell that functions in the
breakdown and resorption of bone tissue). When it is attached to the bone tissue it
produces such acid and enzymes produced by osteoclasts are capable of removing the
inorganic calcium and phosphorus from the bone tissue.
They can also break down organic material, such as collagen, that constitutes
the bone itself. Initially, the bone is broken apart with the minerals still inside of the
tissue and forms osteolytic lesions. Therefore there is continuous bone destruction that
may cause pathologic fracture. Once bone is destructed Calcium will be released in the
bloodstream arising to hypercalcemia and will further contribute to the formation of
kidney stone thus may result to kidney failure.
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Production and release of paraprotein (M protein) from the multiple myeloma into
the blood stream and/or urine The multiple myeloma cells usually produce a large
amount of one type of abnormal antibody. This is known as aparaprotein. This
paraprotein cannot fight infection effectively and often reduces the production of normal
antibodies. Reduction of normal immune function, which causes reduced levels of
normal immunoglobulins and increased susceptibility to infection.
There is also an increase in serum monoclonal antibodies from the production of
Paraprotein that will bind to the serum protein resulting to Hyperviscosity syndrome. It
refers to any state in which there is increased viscosity of the blood. Increased serum
viscosity usually results from increased circulating serum immunoglobulins (eg,
macroglobulinaemia, multiple myeloma) and can also result from increased cellular
blood components (eg, red or white blood cells) in hyperproliferative states - eg,
leukaemias, polycythaemia and thrombocythaemia.The underlying cause of the
hyperviscosity syndrome may be treated with chemotherapy where appropriate.Clinical
sequel of HVS can include congestive heart failure, ischemic acute tubular necrosis,
and pulmonary edema and if left untreated it will result to death.
Another result of proliferation of myeloma cells is the production of Bence Jones
proteins. Bence Jones protein is a monoclonal globulin protein or immunoglobulin light
chain found in the urine. They are found in urine due to the kidneys' decreased filtration
capabilities due to renal failure, sometimes induced by hypercalcemia from the calcium
released as the bones are destroyed or from the light chains themselves. Resulting to
proteinuria or Kidney Failure.
In this type of plasma cell neoplasm, the abnormal plasma cells (myeloma cells)
collect in one location and form a single tumor, called a plasmacytoma. The aim of
treatment is to eliminate the plasmacytoma. The treatment that is used most commonly
for both types of plasmacytoma is radiotherapy. This involves focusing radiation (similar
to X-rays) on the plasmacytoma to kill the malignant cells. The treatment is generally
given over several days to reduce side-effects; each treatment dose of radiotherapy is

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known as a fraction.The addition of chemotherapy to radiotherapy treatment can be

advantageous.
Multiple myeloma remains incurable despite recent remarkable advances in
therapy. Treatment is aimed at preventing or relieving symptoms and complications,
destroying abnormal plasma cells, and slowing progression of the disorder.The most
consistently helpful group of drugs for multiple myeloma is corticosteroids, such as
prednisone, methylprednisolone, or dexamethasone, although many new drugs are
showing great promise. In addition, chemotherapy slows the progression of multiple
myeloma by killing the abnormal plasma cells. Because chemotherapy kills normal cells
as well as abnormal ones, the blood cells are monitored and the dose is adjusted if the
number of normal white blood cells and platelets decreases too much.
Treatment is aimed at reducing the tumor burden, preventing and controlling
complications (e.g., infections, anemia, hypercalcemia, pathologic fractures), and
managing pain. The goal is to maintain as much mobility as possible.
Survival time varies widely depending on certain features, such as kidney
problems, blood levels of certain proteins including beta 2-microglobulin and serum
albumin, and genetic characteristics, at the time of diagnosis and the response to
treatment. Importantly, bisphosphonates to reduce bony complications, substances that
stimulate the production of blood cells (growth factors) to increase the number of red
and white blood cells, and better pain relievers have also greatly improved the quality of
life.

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