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30 Cards in this Set

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1. What cells are essential for specific immunity, immune memory, and Control of Hematopoiesis?

2. What cells are essential to fight bacterial infections?

3. What cells are important in parasitic infections and hypersensitivity reactions?
1. Lymphocytes

2/3 = Granulocytes

2. Neutrophils 3. Eosinophils
4. Macrophages come from _____?

5. What cells are responsible for delivering high concentrations of O2 to the cells?

6. What cells are vital to control hemorrhage?
3. Monocytes

4. Erythrocytes

5. Megakaryocytes --> Platelets / Thrombocytes
Describe the tree of differentiation involved in the various blood cells:
Pluripotent Stem Cells
2 Lines

A. Hematopoietic Stem Cells (Myeloid Cells) --> RBCs, Granulocytes, Monocytes, or Plts

B. Lymphopoietic Stem Cells (Lymphoid Cells) --> T cells or B cells (B cells --> Plasma cells)
What cells are found in Marrow?
Over 90% of nucleated cells = Granulocytes, Monocytes, Megakaryocytes, Erythroblasts (Rubriblasts/Rubricytes)

Also
Macrophages, Lymphocytes, Plasma cells, Stromal cells, and Osteo-blast/clasts
In young animals, hematopoiesis is found ______A_______. As the animal ages, central areas and distal extremities become replaced with ____B____. Productive regions are usually __C__, but the color will vary from __D__ to __D__ depending on the predominant cell type being produced.
A. Throughout the Long and Flat Bones
B. Fat (yellow marrow)
C. Red
D. Pale Yellow to Dark Red
What are two Marrow Sampling Techniques?
1. Aspirate - CYTOLOGIC - collection of cells smeared on slide, stained, and examined.

2. Core Biopsy - HISTOLOGIC - tissue section is prepared (formalin, embedded in paraffin, stained, mounted)
How does one go about Evaluating bone marrow?

(6 Parts)
Assess Cellularity (are there marrow spicules present?)

Does Cellularity appear Increased? (Hypercellular = anemia or infection depending on cell types)

Evaluate Maturation Sequence and Morph of all 3 lines (Erythroid, Myeloid, Megakaryocytes)

Determine Freq. of Whites (Lymphocytes, M-phages, Plasma Cells)

Check for Stable Iron Stores (except in Feline)

Look for others - (Mast, Neoplastic, Osteo-blast/clast)
And what is the final major step in Evaluating Bone Marrow?
Calculate the M:E
(Myeloid to Erythroid ratio)

Normal M:E
Companion Animals = 1:1 - 2:1
Livestock and Horses = ~0.5:1
List 6 indications for a bone marrow aspirate?
1. Unexplained/Persistent Rise or Fall in any particular cell line.
2. Abnormal circulating cells (not fully differentiated cells)
3. Fever of unknown origin
4. Unexplained lab findings (hyper-calcemia/proteinemia)
5. Staging of malignancies (lymphoma, mast cell tumor)
6. Systemic infections.
Bone Marrow Aspirate is only any good if ________
you send it in with a CONCURRENT CBC
List 5 indications to do a Core Biopsy:
1. Bone changes
2. Bone marrow cellularity
3. Bone marrow fibrosis
4. Focal lesions
5. Unsuccessful Aspiration
Erythroid Hyperplasia
Due to: Hemorrhage or Hemolysis
Thus this clinical finding is usually good and indicating a Normal response.

Low Hemoglobin > Hypoxemia > *EPO from Kidneys > ^erythropoiesis in marrow.

Results in Decrease in the M:E
Immature Reds can appear in Circulation.
When can Erythroid Hyperplasia be a bad sign?
Blood Loss:
if acute - Iron stores can make up for the temporary low RBC count

if Chronic - Iron become depleted, blunting the regenerative response and causing a Non-Regenerative Anemia.
Erythroid Hyperplasia with Concurrent Myeloid Hyperplasia
Due to Acute, Very Severe Anemia (eg. IMHA)
M:E slightly decreased or not affected as both lines are increasing.

**Leukocytosis is seen because the rapid decrease in RBCs causes tissue hypoxia -> necrosis -> *Granulopoiesis (ie Myeloid Hyperplasia)
Mild to Moderate Erythroid Hyperplasia w/o Anemia
1. Chronic O2 deprivation (high alt, lung/heart dz)
2. Hyperthyroidism (increase O2 demands)
3. Compensation for Hemolytic Dz

(1+2 may lead to erythrocytosis)
Myeloid Hyperplasia
Increases the M:E (up to 99:1)

Due to inflammation/infection, Stimulated by IL1, IL3, SCF, CSF

Antigen/Endotoxin --> *TCells and Mphages release IL1 and TNF --> Other cells making More Factors

May be a slight left-shift in granulocyte prodxn
Megakaryocyte Hyperplasia
1. Peripheral Destrxn (immune-mediated thrombocytopenia)
2. Loss (hemorrhage)
3. Consumption (DIC)
Other Hyperplasias
Non-Specific Increase
Lymphocytosis, Plasmacytosis, Histiocytosis, Mastocytosis
Hypoplasia
of a marrow line results in peripheral decrease in that cell type - Clinical Signs reflect the function of this missing cell type.
(RBC - weakness, WBC - susceptibility, Plt - Bleeding)
A measurable hypoplasia of one ore more cell lines is reflected in a ____A____ or a ____B____ OR a _____C_____
A. Change in the M:E
B. Decrease/Absence of a particular line
C. Failure to Respond w/appropriate Hyperplasia, despite a peripheral cytopenia.
List 8 Mechanisms of Hypoplasia
1. Anemia of Chronic Dz or Infamm (ACD)
2. Immune-mediated suppression
3. Cytotoxic or Drug-induced
4. Infection (Parvo, FeLV, FIV, Erlichia)
5. Endocrine (Hyperestrogen - generalized; Hypothyroid - erythroid)
6. Iron Def. Anemia
7. Renal Failure (low EPO)
8. Idiopathic
What is the most common mechanism of bone marrow hypoplasia?
ACD - Anemia of Chronic Dz or Inflamm

M:E is normal to slightly high
No evidence of compensation
TNF and IL1 suppress EPO prodxn
TNF inhibits erythroid proliferation
IL1 --> TCell Interferon --> inhibits erythropoiesis
Inflammatory Diseases of Marrow
Not easily recognized in Aspirates because inflamm cells are a normal component of marrow.
Myelodysplastic Syndrome
MDS = ineffective proliferation or hyperplasia of one or more cell lines, resulting in a peripheral cytopenia.

You will see Hyperplasia of lines in the marrow (possibly w/abnormal morph) but no peripheral improvement.

Blast-Cell% is higher than normal (but under 20%, the cut-off point for Leukemia)
Causes of MDS:

In Cats?
In Dogs?
In Others?
Cats - FeLV (red line)

Dogs - likely a Toxin/Drug

Other - very rare
Chronic Myeloproliferative Dz
(and 4 examples)
Very Rare -- High peripheral counts with marrow hyperplasia and normal morphology.

PV - Polycythemia vera (erythro)
ET - Essential thrombocytemia (plt)
CGL - Chronic Granulocytic Leukemia (mature WBCs)
MMM - Myelofibrosis with Myeloid Metaplasia
Dx-ing a Chronic Myeloproliferative Dz
Process of Elimination considering all other causes of:

Erythrocytosis (PV) - dehydration, hypoxia, etc.
Thrombocytosis (ET) - iron def, inflamm, etc.
Neutrophilia (CGL) - inflamm, necrosis, etc.
Marrow Fibrosis (MMM) - neoplasia, marrow necrosis, etc.
Acute Myeloid Leukemia
Signs - anemia, neutropenia, and/or thrombocytopenia

Blood smear for Blast Cells
Myeloid Blasts over 20% = Leukemia

Extremely Poor Prognosis
What are the 3 Lymphoproliferative Dz?
1. CLL - Chronic Lymphoid Leukemia
2. ALL - Acute Lymphoid Leukemia
3. Multiple Myeloma

Difficult/Pointless to distinguish between Stage 5 Lymphosarcoma from ALL
Myelofibrosis
Secondary to Injury, Neoplasia, Inflammation --- impedes aspiration, is thus diagnosed Histologically.

A Primary Myelofibrosis = a Myeloproliferative Dz