multiple myeloma with pathophysiology

Prepared by: Maribec V. Pagaduan

A 69 year old male complained of pain in his lower back upon bending over in his garage.

He worked in a petroleum plant for 15 years.

He also complained of easy fatigability.

A radiograph of the spine shows a compression fracture of the lumbar vertebrae at L2 – L3.

Further evaluation reveals normocytic anemia, hypercalcemia, and a high globulin fraction. Bone marrow biopsy was also done.

Other name: Plasma cell myelomaSecond most common hematologic

malignancy.It affects osseous and non-osseous

tissues.

The cause of myeloma is unknownHigh occurrence among the following:

- Those exposed to radiation warheads

- Myeloma has been seen more commonly than expected among farmers, wood workers, leather workers, and those exposed to petroleum products.

Occurrence: 2-4/100,000Age: Increases with age

Median Age of Px: 65 y/oGender: More men than womenRace: More common in Blacks than in

Caucasians, Asians – low incidence.

RED BONE

MARROW

Composition

1.The PARENCHYME2.The STROMA

- Continuous replacement of old bone tissue by new bone tissue

2 types of cells1.Osteoblasts2.Osteoclasts

Used to determine size and shape of RBCs, WBCs and platelet precursors and to examine various maturational abnormalities.

Gold standard for diagnosing MM

L2-L3 Compression

Non destructive method of inspection

Each specimen under evaluation will have differences in density, thickness, shapes, sizes, or absorption characteristics

Randomly distributed, rounded, punched out lytic lesions throughout the skull.

Patient Normal

WBC 3.4 X 103/uL (3.3-11.0)

Neut 9 % (44-88)

Lymph 27% (12-43)

Mono 4% (2-11)

Eos 0% (0-5)

Baso 0% (0-2)

RBC 3.2 X 106/uL (3.9-5.0)

Reticulocytes 1.% (0.5-1.5)

Hgb 8.6 g/dL (11.6-15.6)

HCT 26.1 % (37.2-50.4)

MCV 81.5 fL (79-99.0)

MCH 26.8 pg (26.0-32.6)

MCHC 32.9 g/dL (31.0-36.0)

Plts 110 thousands/uL (130-400)

Test Patient Normal

Glucose 90 mg/dL (65-110)

Creatinine 1.9 mg/dL (0.7-1.4)

BUN 29 mg/dL (7-24)

Uric Acid 9 mg/dL (3.0-8.5)

Cholesterol 199 mg/dL (150-240)

Calcium 12 mg/dL (8.5-10.5)

Protein 10.9 g/dL (6-8)

Albumin 3.7 g/dL (3.7-5.0)

LDH 270 U/L (100-225)

Alk. Phos. 210 U/L (30-120)

AST 50 U/L (0-55)

GGTP 35 U/L (0-50)

Bilirubin/Bil. Direct 0.7 mg/dL/(.11 mg/dL) (0.0-1.5)/(.02-18)

Test

Patient Normal

pH 6 (5.0-7.5)

Protein 3+ (Neg)

Glucose Neg (Neg)

Ketone Neg (Neg)

Occult blood Neg (Neg)

Color Yellow (Yellow)

Clarity Clear (Clear)

Sp. Grav. 1.050 (1.010-1.055)

WBC 3/HPF (0-5)

RBC 1/HPF (0-2)

A process of separating electrically

charged particles in solution by passing an electric current through the solution

Particularly used to determinewhether the humoral immunity function normally or not.

Albumin 1 2

MAJOR CRITERIAI.Plasmacytoma by biopsyII.>30% marrow plasmacytosisIII.Monoclonal gammopathy Serum: IgG > 3.5 g/dL, IgA >2 g/dL Urine: >1 g/d of Bence Jones Proteins

MINOR CRITERIAA.10-30% marrow plasmacytosisB.Monoclonal gammopathies with lower values than aboveC.Lytic bone lesionsD.Suppressed normal immunoglobulins

Durie-Salmon Staging SystemStage Criteria Estimated Tumor

Burden, x 1012 cells/m2

I All of the following: 1. Hemoglobin >100 g/L (>10 g/dL)

2. Serum calcium <3 mmol/L (<12 mg/dL) 3. Normal bone x-ray or solitary lesion 4. Low M-component production a. IgG level <50 g/L (<5 g/dL) b. IgA level <30 g/L (<3 g/dL) c. Urine light chain <4 g/24 h

<0.6 (low)

II Fitting neither I nor III 0.6–1.20(intermediate)

III One or more of the following: 1. Hemoglobin <85 g/L (<8.5 g/dL)

2. Serum calcium >3 mmol/L (>12 mg/dL) 3. Advanced lytic bone lesions 4. High M-component production a. IgG level >70 g/L (>7 g/dL) b. IgA level >50 g/L (>5 g/dL) c. Urine light chains >12 g/24 h

>1.20 (high)

Age: 69 y/o, Male, Hx of working in a petroleum plant

DNA is damaged during the development of stem cell into a B – cell

Development of malignant plasmablasts

Produce adhesive molecules and bind to Bone Marrow Stromal Cells

Malignant plasmablast grows into malignant plasma cells

Uncontrolled proliferation of malignant plasma cell clones

Formation of Plasmacytomas

Production of Paraproteins (M-protein)

Production of Bence Jones

Protein


Compression of surrounding bone

tissue, bone marrow and nerve

endings

PAIN

↓ Hematopoesis

Release of IL-6 and TNF

Recruitment and activation of osteoclasts

Osteoclasts attach to bone tissue

Protein digesting enzyme

Acids

Digestion of collagen and fibers

Dissolves bone minerals

PUNCHED-OUT OSTEOLYTIC LESIONS

Continuous bone destruction

PATHOLOGIC FRACTURE

Calcium is released and

enters the bloodstream

HYPERCALCEMIA

Destruction of Bone marrow

stem cells

↓osteoblasts

↓bone deposition

↓Hematopoiesis

↓RBC

ANEMIA

↓Megakaryocytes

↓Platelets

↑Susceptibility to bleeding

↓WBC

↑ Susceptibility to infection

Easy fatigability

THROMBOCYTOPENIA

Leukopenia










Protein


↑ Serum Monoclonal Antibodies

Normal Plasma cell breakdown

↓ Normal Antibody production

HYPERVISCOSITY SYNDROME

Binds with other serum protein

Disrupted antibody mediated immunity

↑ Susceptibility to infection

↑ Susceptibility to bleeding










Protein

Production of Bence Jones Protein

Blockage of tiny kidney tubules

Excreted in urine

↓erythropoietin

PROTEINURIA

↓ elimination of nitrogenous

waste

UREMIA

ANEMIA

↓RBC Production

Glomeruli filters large amounts of

Bence-Jones Protein

Proteinaceous inclusion bodies

accumulates in the tubules

Cellular degeneration and impairment of kidney/tubular

function

Chronic PainActivity intoleranceRisk for InfectionFear/Anxiety

Trials of Arsenic Trioxide in Multiple MyelomaMohamad A. Hussein, MD

Anatomy and Physiology by Tortora, 11th ed. Clinical Physiology by Moran Campbell Pathophysiology By Porth, 4th ed. Harrison’s Principles of Internal Medicine, 17th ed. Wintrobe’s Clinical Hematology, Blood and Bone Marrow Pathology by

Wickramasinghe and McCullough

multiple myeloma with pathophysiology

Documents