Leukopoiesis, WBC Differentiation, and Lymphocyte Function Flashcards by Kershia Mukoro

How many WBCs are produced daily?

1.5 Billion

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What stem cells give rise to WBCs?

Myeloid stem cells and lymphoid stem cells

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Myeloid stem cells and lymphoid stem cells originate from?

Pluripotent stem cells

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The WBC maturation cycle is more complex than the RBC maturation cycle? T/F

True

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How many WBCs are produced for 1 erythrocyte?

5 (4)

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Neutrophils, Basophils, Eosinophils, and Monocytes are produced by what type of stem cell?

Myeliod stem cells

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Lymphoid stem cells give rise to?

B cells and T cells

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Where are B and T cells produced?

Bone marrow and thymus

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The word granulocytic applied to?

Only granulated WBCs

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Which of the following applies to WBCs of all stages? a. Myelocytic b. Leukocytic c. Granulocytic d. All of the above

b. Leukocytic

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Which of the following is synonymous with granulocytic? a. Myelocytic b. Leukocytic c. Granulocytic d. All of the above

b. Myelocytic

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What do the majority of leukocytes contain?

Granules with enzymes used for digestion and destruction.

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Where are Leukocytes located?

Bone Marrow, Circulation, Tissues, Some storage in the spleen

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These defend against bacteria, viruses, fungi, and foreign substances.

Leukocytes

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Hematopoeisis is?

Process of cell production that maintains leukocytes, erythrocytes and platelets (3 diff cell lines)

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Describe Leukopoiesis?

Process of generating WBCs (leukocytes)

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Distinguish between marginating and circulating pools of leukocytes?

Circulating Pool - in the bloodstream Marginating Pool - in the vessel endothelium (inner layer of blood vessels)

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The morphology of what features are used to differentiate WBCs?

Cell Size
N:C ratio

3 . Chromatin pattern (presence/absence of nucleoli)

Cytoplasmic quality (presence/absence of granules AND types of granules present).

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What are the granulocytes?

Eosinophils Basophils Neutrophils

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What are the agranulocytes?

Monocytes

Lymphocytes

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What are the 5 stages of (precursor) maturation from immature to most mature for neutrophils, basophils and eosinophils?

Myeloblast N:C 6:1
Promyelocyte N:C 3:1
Myelocyte N:C 2:1
Metamyelocyte N:C 1:1
band / eosinophilic band / basophilic band

Final Form: Segmented neutrophil / basophil / eosinophil

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What are the stages of Monocytic Maturation?

Monoblast N:C 6:1
Promonocyte N:C 3:1
Monocyte N:C 1:1

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What are the 3 stages of Lyphocytic Maturation?

Lymphoblast N:C 4:1
Prolymphocyte N:C 3:1
Small Lymphocyte N:C 4:1 / Large Lymphocyte N:C 3:1

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Describe eosinophilic granules?

Round, large, dirty orange

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Describe basophilic granules?

large, dark blue

Describe Neutrophilic granules?

Very fine, pinkish color and begin near nucleus

At what stage can granulocytes be distinuished?

Myelocyte stage

What is the function of neutrophils?

Seek, ingest, kill bacteria phagocytocis

What is the most numerous WBC?

Neutrophils

What is the function of eosinophils?

Respond to allergic and parasitic reactions

What is the function of basophils? What do they contain?

Respond to hypersensitivity and reactions and inflammation Contain: Herparin and hystamine

What are the primary Lymphoid organs?

Bone Marrow and thymus

What are the secondary organs of the lymphatic system? (4)

Spleen, Peyer's patches, lymph nodes, tonsils

What are the responsibilities of the lymphatic system?

**F**luid balance **L**ymphopoiesis **A**ntibody generation **B**lood filtration

Describe lymph fluid?

Thin, clear, derived from plasma

How is lymp circulated?

Circulates from respiration muscle movement nearby vessel pressure

What are the primary locations of lymphopoiesis?

Bone marrow: B cells Thymus: T cells

What lymphoid stem cells migrate to the thymus? (2)

T helper cells T supressor cells

What lymphiod cells stay in bone marrow?

B cells NK cells

60 - 85% of lymphocytes Cell mediated immunity mature in the thymus

T Cells

Once stimulated by antigen contact T cells?

CD4 (T helper cells) help promote antibody production and assist with immune intracellular pathogens CD8 (T killer cells) cytotoxic elimination of non-self by promoting enzyme activity

10 - 20 % of lymphocytes Mature into plasma cells that produce anibodies Humoral immunity may be stimulated toward a particular immune response

B Cells

\<20% of lymphocytes role in resisting bacteria, viruses and fungi do not require stimulation

Natural Killer (NK) cells

Foreign bodies emit signals sensed by neutrophils These signals are used to move towards the site of invasion

Chemotaxis

Neutrophil receptors attach to foreign body. this attachedment is enhanced after body has been opsonized with complement or Igs

Opsonization

Opsonized foreign body is _____ by nuetrophil and \_\_\_\_\_\_ Neutrophilic granules ______ \_\_\_\_\_\_\_ which contain elements that destroy foreign body and the neutrophil too.

ingested, killed release contents

Leukocytosis

Absolute increase in total WBC count

What is a **Left Shift**?

Exaggerated response to infection and inflammation, which may include: * toxic vaculozation * Dohle bodies * toxic granulation * immature cells younger than metamyelocyte but rarely blasts

What is **Leukoerythroblastic picture**?

Peripheral smear contains immature WBCs, nRBCs, and platelet abnormalities. Significant feature of myeloproliferative disorders

In which stage of neutrophilic maturation are specific secondary granules first seen?

Myelocyte

These following condistions cause what quantitative change in which WBC line? Infections (bacterial) Inflammatory response Stress response Malignancies chemical assault

Neutrophilia (increase)

These following condistions cause what quantitative change in which WBC line? Drugs chemotherapy autoimmune disease

Neutropenia

These following condistions cause what quantitative change in which WBC line? allergies skin disease parasitic disease transplant rejection myeloproliferative disorders

Eosinophila (increase)

These following condistions cause what quantitative change in which WBC line? Acute infections ACTH Bone Marrow Aplasia

Eosinopenia

These following condistions cause what quantitative change in which WBC line? Myelo proliferative disorders hypersensitivity reactions Ulcerative colitis Chronic inflammatory conditions

Basophila (increase)

These following condistions cause what quantitative change in which WBC line? Steriod treatment inflammation

Basopenia

These following condistions cause what quantitative change in which WBC line? Chronic infections (TB) Malignancies Leukemias w/ stong monocytic component bone marrow failure

Monocytosis

These following condistions cause what quantitative change in which WBC line? Autoimmune processes Hairy cell leukemia

Monocytopenia

These following condistions cause what quantitative change in which WBC line? Normal in children 4 - 4 months old Viral (CMV, EBV, HIV) Leukemias

Lymphocytosis

These following condistions cause what quantitative change in which WBC line? HIV malnutrition chemotherapy radiation renal failure

Lymphocytopenia

Infection, Human Erlichiosis, and Megaloblastic processes are _______ conditions causing qualitative WBC changes.

Acquired

* May-Hegglin Anomaly * Alder-Reily Anomaly * Palger-Huet Anomaly * Chediak-Higashi Syndrome * Lipid Storage Diseases The above are all __________ conditions causing qualitative WBC changes.

Hereditary

Left shift: * increase in bands and metamyelocytes in the peripheral smear. * larger than normal basophilic granules within the cytoplasm of neutrophils, bands, and metamyelocytes. Resemble primary granules or promyelocytes Toxic vacuolization: * Round, clear spaces within the granulite cytoplasm * Dohle bodies * round, oval light blue staining found in the cytoplasm * Remnants of RNA

Infection

* Notable white cell inclusion cause by two varieties of Rickettsia-like bacteria: * Erlichia chafeenis * Anaplasma phagocytophilum * Common to both illnesses is low WBC count, elevated liver enzymes, and thrombocytopenia. Inclusions may be seen in the granulocyte or monoytes from the bone marrow.

Human Erlichiosis

* Hypersegmentation * Folic acid deficiency * Pernicious anemia * B12 deficiency

Megaloblastic Processes

* Autosomal Dominant * Thrombocytopenia and giant platelets (poorly granualated) * Larger Dohle bodies found in cytoplasm of neutrophils

May-Hegglin Anomaly

* Rare genetic disorder * Prominent depostion of granules in every cell line * Lipid deposition in the cytoplasm

Alder-Reilly Anomaly

* Most common (dominant trait) * 70 - 95% hyposegementation * Heterozygotes: dumbell shaped nuccleus * Homozygotes: nucleus is spherical * Pseudo - _____ \_\_\_\_\_ - myeloproliferative disorders, severe infections and leukemias.

Pelger-Huet Anomaly

* Rare autosomal recessive disorder of neutrophilic granuels * giant purple grey cytoplasmic granuels * lymphocytes and monocytes nay show a signle red granule in cytoplasm * WBCs show reduced chemotaxis and bactericidal killing function * hepatospenomegaly and liver failure may develop * abnormal bleeding time * **Affected children may show albinism and photophobia**

Chediak-Higashi Syndrome

Lipid storage diseases are the result of?

a missing or inactive strategic enzyme caused by a singele gene deletion

* deficiency of the enzyme **beta-glucocerebrosidase** * leads to accumulation of glucocerebrosidase mostly in monocytes /macrophages * characterized by severe bone pain

**Gaucher's disease** **(accumution causes Gacher cells)**

* Deficiency of the enzyme **sphingomyelinase** * enlarged liver and spleen * thrombocytopenia * **sea-blue histocytes** in bone marrow * macrophages have globular cytoplasm

**Neimann-Pick Disease**

* deficiency of the enzyme **hexaminosidase A** * No large identifiable bone marrow cells * can be tested prenatally * deafness and blindness * seizure * death in a few years

**Tay-Sachs Disease**

**Normal for young children 1 - 4 years** Differential will show reversal of lymphocytes to segmented neutrophils normal morphology

**Relative lymphocytosis**

Reactive Lymphocytosis represents?

a response to **viral infection** such as EBV and CMV

What is the most common disease showing variation in lymphocytes?

Mononucleosis

Infectious mononucleosis is caused by _______ \_\_\_\_\_\_\_, which infects __ \_\_\_\_\_\_\_\_\_\_.

Epstein-Barr Virus B Lymphocytes

What are some symptoms of mononucleosis?

Sore throat fatigue anorexia fever enlarged lymph nodes

What 2 ways is mononucleosis diagnosed?

rapid agglutination tests or careful examination of smear

Reactive lymphocytes (ATL) charateristics?

Scallop red cells and abundant royal blue cytoplasm

What virus is endmic worldwide?

CMV

What is CMV isolated from?

respiratory secretions urine semen cervical secretions

\_\_\_\_\_\_\_ of blood donors show anti-CMV titres?

40 - 90%

Donor blood for infants must be ?

CMV Negative

Seen in lipid storage disease, macrophage with globular cytoplasm

Nieman Pick Cell

change can be seen during serious infections (2)

Toxic granulation Toxix vacuolization

seen in lipid storage disease, crinkled tissue paper appearance of cytoplasm

Gaucher cell

Seen in megaloblastic anemias

Hypersegmented neutrophils

WBC reaction can be seen in mononucleosis?

Reactive Lympocytosis

giant-grey green cytoplasmic granules

Chediak-Higashi

Giant platelets and Dohle bodies in cytoplasm

May-Hegglin Anomaly

Hyposegmentation seen in the majority of neutrophils

Pelger-Huet Anomaly

What is the most common leukemia affecting adults?

AML

In an AML smear what would be seen? Blasts Auer rods Pseudo Pelger-Huet cells possible NRBCs\* All of the above

All of the above

What is the prognosis for AML?

fatal in 2-3 months w/o treatment

What acute leukemia affects children \<10 and peaks between 2- 6 years old?

ALL

T/F the peripheral smear in ALL is: Lab: elevated WBC count close to 100% lymphoblasts and lymphocytes

True

ALL Prognostic factors

What are the 4 main WHO groups of AMLs?

* AML w/ recurrent cytogenetic abnormalities * AML w/ myelodsplasia * Therapy related AMLs and MDS * AML not otherwise specificied

What is the WHO requires what blast percentage?

\>20% in blood or bone marrow

What is Dysplasia?

the abnormal maturation of cells in bone marrow

What dysplastic features are seen in AML w/ Myelodysplasia? * Platelets

May exhibit micromegakaryocyte with one lobe instead of multiple lobes

What dysplastic features are seen in AML w/ Myelodysplasia? * Erythroid

Nucleated red cells megaloblastic features cytoplasmic vacuoles ringed sideroblast

What dysplastic features are seen in AML w/ Myelodysplasia? * Neutrophils

Hypogranulation Hyposegmentation or Pseudo-pelgeriod Bizzarre segmented neclei

What are the 4 WHO classfications on AML that do not fit into other catogories and is primarity based on morphology and cytochemistry?

AML, w/ Maturation Acute Monoblastic and Monocytic Leukemia Acute Erythroid Leukemia Acute Lymphoblastic Leukemia

A clinical feature of acute leukemia is leukemic cells?

Ovewhelm bone marrow * Anemia (normocytic-normochromic) * Thrombocytopenia

AML Not otherwise specified: * \>80% monocytic origin * ________ predominance of blasts * ________ predominance of promonocytes

AML, w/ maturation Acute monoblastic leukemia Acute monocytic leukemia

AML Not otherwise specified * The most common leukemia: 30-45% of AML * \>10% maturation beyond promyelocyte * monocytic compenent \<20% noneythroid cells

AML, w/ maturation

A hallmark clinical feature is extramedullary disease and ginigival hypertrophy

Acute monoblastic and acute monocytic leukemia

AML Not otherwise specified: * Abnormal proliferation of erthroid precursors * \>50% or BM cells are erthroid and at least 30% are myeloblast * Pure _____ leukemia is \>80% precursors

Acute Erthroid leukemia Erythroid

AML Not otherwise specified: * most rare form of the AMLs * at least 20% of blasts in BM are megakaryoblasts

Acute Megakaryoblastic Leukemia

What are the two WHO groups of Lymphoblastic Leukemias?

* Precusor B cell * Precursor T cell

Lymphoblastic Leukemia occurs in _____ \_\_\_\_ and \_\_\_\_\_ * _____ of BM cells are lymphoblast Lymphoblastic Lymphoma occurs in _____ \_\_\_\_\_ * ______ \_\_\_\_\_ and _____ of BM are lymphoblast

BM and blood, \> 25% Lymph tissue, mass lesion and \<25%

AML with recurrent Genetic abnormailities: * Monoblasts and promonocytes in peripheral blood and BM * often show pseudopodia * fine nuclear chromatin with 1 or more nuclei * azurophilic granules * cytoplasmic vacuoles

AML w/ 11q23

AML with recurrent Genetic abnormailities: * hypergranualar promyelocytes * multiple auer rods * some mocrogranular promyleocytes * assocuated w/ DIC

Acute promyelocytic leukemia t(15:17)

AML with recurrent Genetic abnormailities: * hypergranualar promyelocytes * multiple auer rods * some mocrogranular promyleocytes * assocuated w/ DIC

Acute promyelocytic leukemia t(15:17)

AML with recurrent Genetic abnormailities: * increased eosinophils * varios stages of myelocytic, monocytic, and eosinophilic maturation * high remission rates

AML inv (16)

AML with recurrent Genetic abnormailities: * Large myeloblast * auer rods common * young WBC seen in smear * eosinophils increased * good long-term survival

AML t(8:21)

What are Chronic Myeloprolferative DIsorders (CMPDs)?

The are a group disorders that are clonal malignancies (disease arising from single cell line).

What are the cell lines affected in these CMPDs? * CML * PV * IMF * ET

* Granulocytic * Erythrocytic * Fibroblast/All * Megakaryocytic

What is the age of onset for CML?

20 - 50 years

CML shows marked neutrophil leukocytocis, with a WBC amouting?

WBC \>50,000

90 - 95% of CML patients have what chromosome? Explain how it is created and what gene results from this mutation, and the effect it has.

Philedelphia (Ph) Chromosome Results from translocation from chromosome 22 to chromosome 9 forming BRA-ABL fusion gene. This gene results in increased tyrosine kinase activity, which prevents apoptosis, creating an immortal cell line. (excess cell prolifereation and production)

Describe the clinical features of CML? (3)

Can be asymptomatic Normocytic/normochromic anemia 3 Phases: chronic, accelerated, and blast.

The M:E ratio in CML can be as high as?

25:1 | (10:1 in BM)

Describe the Peripheral Blood and Bone Marrow for the **Chronic** phase of CML?

PB * blasts \>2% * throbocytosis BM * blast \<5% * M:E ratio 10:1

Describe the Peripheral Blood and Bone Marrow for the **Blast** phase of CML?

PB * blasts \>20% * throbocytopenia BM * blast\>20% * Large clusters of blasts * Marked dysplasia on all 3 cell lines

Describe the Peripheral Blood and Bone Marrow for the **Accelerated** phase of CML?

PB * basophils \>20% * throbocytopenia BM * Dysplasia * Fibrosis

Leukocyte Alkaline Phosphatase (LAP) differentiates CML from a leukemoid reaction, what is the LAP reference range and score in CML?

Ref 20 - 100 CML \<13

3 Treatments for CML?

* Myelosupressive surgery to inhibit BCR-ABL tyrosine kinaase * Leukophoesis - cell seperator to decrease WBC count * Allogenic BM transplant

CML has a poor prognosis based on what factors? (6)

* age * phase of CML * amount of blasts in peripheral blood * size of spleen * marrow fibrosis * general health

T/F There is no treatement for acute CML?

True

Which phase of CML is reponsive to treatment?

Chronic phase

What is the age of onset for **Polycythemia Vera**?

60 - 70 years old

Describe the BM in PV?

Hypercellular with Hyperplasia

What is PV? and what does it lead to?

Clonal disorder: overproductions of mature RBCs, WBCs, and PLTs increaed Hgb, HCT, and RBC mass which increases blood viscosity and predisposition to arterial and venous thrombosis

What mutation is present in PV and what percentage of patients have it?

90% JAK2 mutation

What does the JAK2 mutation do?

activates a kinase that sends a signal to cell to proliferate leading to increased RBCs.

Clinical features of PV are * Major symptoms related to and increase in red cell mass, which are? (3) * Increased blood cell turnover (1) * Abdominal pain (1)

* Hypertension, hyperviscosity, vascular abnormalities * headache, light headedness, blurred-vision * thrombosis * Hyperuricemia, gout, stomach ulcers * hepatomegaly / splenomegaly

What are 2 diagnostic characteristics of PV?

* Increase in all 3 cell lines * Neutrophilia with shift to the left and basophili * LAP score elevated * Serum erythropoetin low compared to secondary erthrythocytosis

What is the most significant diagnostic finding in PV that distinguishes it from secondary and relative erythropoiesis (3)?

* Increase in Red Call Mass * Splenomegaly w/ increase in leukocytes and platelets * JAK2 mutation

What is the goal of treatment in Polycythemia Vera?

decrease HCT

What are treatments for Polycythemia Vera? (2)

* Therapeutic Phlebotomy * Low dose apsrin to manage thrombosis risk

Which chronic myeloproliferative disorder has a median survival time of 10 years?

Polycythemia Vera

What is **Idiopathic myelofobrosis** (IMF) is charaterized by?

Bone marrow fibrosis, proliferation of megakaryocytic, granulocytic and extramedullary disease.

Which CMPD is characterized by extramedullary disease?

Idiopathic Myelofibrosis (IMF)

What are 3 clinical features of Idiopathic Myelofibrosis (IMF)?

* Early stages asymptomatic * Pancytopenia * **Osteosclerosis**

A typical peripheral smear in Idiopathic Myelofibrosis (IMF) will have what RBC?

Tear drop

How is Idiopathic Myelofibrosis (IMF) diagnosed? (6)

* CBC * Spleomegaly * BM fibrosis * Leukoeythroblastic picture * No increase in red cell mass * no philedelphia chromosome

T/F There are no treatments to reverse the process of myelofibrosis?

True

Hydroxyurea is used in Idiopathic Myelofibrosis (IMF) as a cytoreductive therapy to control? (3)

* Leukocytosis * Thrombocytosis * Organomegaly

Which CMPD has the worst prognosis? Survival?

Idiopathic Myelofibrosis (IMF) 3-5 years

What is Essential Thrombocythemia?

CMPD charaterized by disorder of multipotenial stem cell

Essential Thrombocythemia can affect ___ \_\_\_\_ cell lines.

**All 3** cell lines

In what cell line is the main increase in Essential Thrombocythemia?

Megakaryocytes

How does Essential Thrombocythemia affect PLTs?

Increase in PLTs due to hypersensitivity of megakaryocytes to cytokines and thrombin

What is a hallmark diagnostic criteria of Essential Thrombocythemia?

Unexplained elevated PLT count

Hydroxyurea, anagrelide, or alfa-interferon are used in treament of Essential Thrombocythemia to ? (2)

* reduce PLT count * decrease risk of vaso-occlusion or hemmorhage

What treament is used in severe cases of Essential Thrombocythemia?

plateletpheresis

What is the survival rate for Essential Thrombocythemia?

10 years for 64 - 80%

Most patients with Essential Thrombocythemia die from?

thrombotic complications

Clonal Lyphoproliferative disorders primarily affect what age group?

Elderly

Clonal Lymphoproliferative Disorders are ?

Clonal malignant proliferation of B and T lymphocytes

Clonal Lymphoproliferative Disorders are diagnosed by? (2)

* Flow cytometry * chromosoml analysis / molecular

Chronic Lymphocytic Leukemia (CLL) is clonal proliferation of?

B lymphocytes

Caused by chromosomal abnormalities Small lymhocytes accumulate in the spleen, lymph nodes, bone marrrow, and can spill out into peripheral curculation.

Clonal Lymphocytic Leukemia (CLL)

Clonal Lymphocytic Leukemia (CLL) Peripheral smear is? (2)

* nearly exclusively small lymphocytes with few lymphoblasts * smudge cells present

Clonal Lymphocytic Leukemia (CLL) Treatment?

* Irradiation or enlarged spleen and lymph nodes * Drugs to reduce lymphocyte burden

Clonal Lymphocytic Leukemia (CLL) mature lymphs are?

non-fucntional

In 80% of Clonal Lymphocytic Leukemia (CLL), what gene is present?

anti-apoptosis gene BCL 2

hypogammaglobinemia is commin in?

Clonal Lymphocytic Leukemia (CLL)

What is a rare B cell malignancy?

Hairy Cell Leukemia

Hairy Cell Leukemia - what causes a dry tap?

BM becomes filled with fibrotic material and BM cannot be aspirated.

What stain is used in diagnosis of Hairy Cell Leukemia? What happens when stained?

Tartrate-resistant acid phosphatase (TRAP) Hairy cells are strongly posisitive and stay positive tartrate acid is added, while other clls become negative.

What is **Sezary Syndrome**?

T cell lymphoma w/ mycosis fungoides

Sezary Syndrome manifests?

Cutaneous manifestation

What cell is being described? * Large cells * Oviod, clefted or folded nucleus * Very smooth homogenous chromatin pattern * May be mistaken for monocytes

Sezary Cells

Describe cause of Hodgkin's Lymphoma? how is it diagnosed?

Singel cervical lymph node becomes firm to touch and does not dissapear, Lymph node biopsy

What cell is being described, where is it located, and which cancer is it unique to? * Large * multinucleated * resembles "owls eye"

Reed-Sternberg cell in bone marrow Hodgkin's lymphoma

Non-hodgkins lymphoma is is 3X more common than hodgkin's and does not have Reed-Sternberg Cells? T/F

True

Plasma cell evolves from?

B lymphocyte

What are the 3 pathways of **Multiple Myeloma**?

1. **Acceleration** of plasma cells in BM 2. **Activation** of bone reabsorbtion factors or **Osteoclasts** 3. **Production** of an abnormal monoclonal protein

In what stage of Multiple Myeloma will the following present: * May develop colorless inclusions called **Russell bodies** or other crystalline inclusions * Flame cells may be seen in IgA myeloma

Acceleration on plasma cells in BM

In what stage of Multiple Myeloma will the following present: * increase in osteoclast activity * bone loss *

Leukopoiesis, WBC Differentiation, and Lymphocyte Function Flashcards

(186 cards)