Hemolymphatic Dz (Bone Marrow, Thymus, Spleen, LN)

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123 Terms

1
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Define hematopoiesis

Bone marrow production of cells (myeloid and lymphoid) that is based on peripheral need

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Young animal bone marrow characteristics

More active red tissue, less fat

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Adult animal bone marrow characteristics

More inactive fatty tissue but there are still sites for hematopoiesis. Extra-medullary hematopoiesis occurs in the spleen

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Regenerative anemia clincal/pathological findings

Icterus, splenomegaly, hemorrhage

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Regenerative anemia bone marrow findings

Erythroid hyperplasia

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Non-Regenerative anemia clincal/pathological findings

Myelofibrosis/bone marrow disease, pallor

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Non-Regenerative anemia bone marrow findings

Absence of erythroid precursors/cytosis of other lineages

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Causes of non-regenerative anemia

-infectious

-toxins

-medications, estrogens

-CKD

-iron deficiency

-neoplasia

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What is aplastic anemia?

Decrease in red and white blood cells leading to pallor, thrombocytopenia, neutropenia, and petechiae/echymoses

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Infectious causes of aplastic anemia

-Ehrlichia (dogs and cats)

-Parvovirus (dogs and cats)

-FeLV/FIV (cats)

-EIA (horses)

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What is a therapeutic cause of aplastic anemia in dogs?

Estrogen administration

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Main lesion of myelofibrosis

Bone marrow fibrosis with macrophages with iron pigment

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What are the 3 mechanisms for myelofibrosis development?

1. Scar formation after necrosis

2. High concentration of growth factors with bone marrow injury or activation

3. Idiopathic

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What are 3 causes of bone marrow necrosis leading to myelofibrosis?

1. Neoplasia (leukemia/metastatic)

2. Infectious (FeLV/sepsis)

3. Toxins

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What are the toxins leading to necrosis and myelofibrosis?

-carprofen

-chemo

-estrogen

-metronidazole

-mitotane

-phenobarbital

-heavy metals

-irradiation

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Serous atrophy of fat lesion and main cause

Lesion = gelatinous transformation of bone marrow

Cause = starvation/emaciation

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Causes of non-neoplastic lymphocytosis in dogs and cats

o Age/antigenic stimulation in cats

o Epinephrine in cats

o Chronic infection

o Ehrlichia canis

o Addison's disease

o Hyperthyroidism in cats

o Paraneoplastic lymphocytosis

o Cattle = Bovine Leukosis Virus (BLV)

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Acute leukemia

-Poorly differentiated

-CD34 expression

-Very poor prognosis (9-56 days)

->20% blast cells in marrow or blood

-Pancytopenia (anemia, neutropenia, thrombocytopenia)

-Median age 7-8 years but wide range in dogs

-Necropsy = pale mucous membranes, bone marrow highly cellular but pancytopenia, splenomegaly, lymph node involvement

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Chronic leukemia

-CD8 expression (T cell)

-CD21 expression (B cell)

-Often has incidental lymphocytosis

-Necropsy = splenomegaly, anemia, lymphadenopathy, highly cellular bone marrow

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Negative prognostic factors in B cell CLL

-Boxers have shorter survival time

-High lymphocyte count >60,000 = shorter survival

-Higher Ki-67 = shorter survival

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Explain the benefits of using flow cytometry in cases of lymphocytosis in dogs and cats

o Distinguishes homogenous from heterogenous expansions

o Identifies aberrant antigen expression

o Provides prognostic information

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List three clinical abnormalities that can be seen with multiple myeloma

o Hyperglobulinemia (overproduction by neoplastic plasma cells)

o Hypercalcemia (bone osteolysis)

o Pancytopenia (neoplastic plasma cells replace the normal cells)

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What abnormality would you except in the bone marrow in a dog with MM?

Markedly increased plasma cells in the bone marrow (>20-30%)

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Identify which cell is infected in equine infectious anemia

Macrophages

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How does thrombocytopenia and anemia develop in EIA?

Immune mediated hemolysis/destruction of platelets

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THYMUS SECTION

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List 3 viral diseases in dogs or cats that can affect the thymus

o Parvovirus (causes injury AND necrosis)

o Distemper virus

o FIV

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List 3 viral disease in other species that can affect the thymus

-EHV-1

-BVDV

-PCV-2

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What is the cause of Post-weaning multi-systemic wasting syndrome?

Porcine Circovirus-2

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What inflammation is present with PCV-2?

Granulomatous inflammation with multinucleated cells with cytoplasmic viral inclusions

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What pathology is seen with PCV-2?

• Thymic enlargement

• Lymph node enlargement

• Interstitial pneumonia

• Poor body condition

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Define the neoplastic cell of a thymoma

Neoplastic epithelial cells

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3 paraneoplastic syndromes with a thymoma & pathophysiology

Myasthenia gravis and megaesophagus — defective antigen presentation leading to auto-antibodies against AchRs, neuromuscular dysfunction in esophagus

Thymoma associated lymphocytosis — expansion of non-neoplastic T lymphocytes in response to the tumor. Note that this is different from lymphoma because lymphoma is neoplastic lymphocyte proliferations.

Exfoliative dermatitis — immune mediated attack on epidermal cells

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What types of cells can you see in an aspirate of a thymoma?

Double positive T cells (heterogenous population on flow cytometry)

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Differentials for a cranial mediastinal mass

o Lymphoma

o Thymoma

o Hemangiosarcoma

o Neuroendocrine tumor

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Cattle thymic lymphoma

-less than 2 years old

-NOT associated with BLV

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Cats thymic lymphoma

-typically 1-3 years old

-CAN be associated with FeLV/FIV

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Dogs thymic lymphoma

-mean age 8 years

-hypercalcemia common

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Goats thymic lymphoma

-3 years of age

-mediastinal involvement frequent

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Pigs thymic lymphoma

-less then 2 years old

-spontaneous

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Thymoma vs. Thymic Lymphoma

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SPLEEN SECTION

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Recognize gross photos of diffuse enlargement and nodular enlargement of the spleen

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List non-neoplastic causes of diffuse soft enlargement of the spleen

Splenic entrapment/volvulus/torsion

Barbiturate euthanasia/anesthesia/sedation

Acute hyperemia/septicemia (anthrax, salmonella, erysipelothrix)

Acute hemolytic anemia (babesiosis, hemolytic crises in EIA, IMHA)

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Why does acute hyperemia/septicemia cause splenomegaly?

this occurs because the number of pathogenic bacteria in circulation exceeds capacity of the splenic macrophages

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What is a typical component of soft expansions of the spleen?

Blood

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What species are primarily affected by anthrax?

Ruminants (peracute hemorrhage and death)

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What is the pathogenesis of anthrax?

1. Ingestion, inhalation, or wound

2. Endospores germinate in macrophages for 1-14 days

3. Spread to lymph nodes and systemic circulation

4. Toxins lead to decreased phagocytosis, increased capillary permeability (edema), and delayed clotting

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What can be seen on impression smears of the spleen in anthrax?

Large gram + rods

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What should be done to manage an outbreak of anthrax?

-Carcasses, bedding, feces, etc must be cremated or deep burial

-Vaccinate exposed animals to contain and prevent disease

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List three differentials for nodular, soft, enlargement of the spleen

1. Hematomas

2. Hemorrhagic infarcts (classical swine fever)

3. Neoplasia (hemangiosarcoma)

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Important note about classical swine fever and african swine fever

African swine fever cause diffuse soft splenomegaly but often the lesions are indistinguishable from classical swine fever

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Tumor cell type hemangiosarcoma

Endothelial cells

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3 breeds commonly affected with hemangiosarcoma

-Golden retrievers

-German shepherds

-Portuguese water dogs

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What are the two primary sites of hemangiosarcoma?

1. Spleen

2. Right auricle of heart

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Hemangiosarcoma gross changes

single or multifocal to coalescing dark red-purple masses which are variably bloody/cavitated to solidly cellular on cut section

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Hematomas gross changes

red to dark red, soft, bulging, usually solitary mass of varying size

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Hemorrhagic infarcts gross changes

wedge shaped hemorrhagic lesions (chronic = pale)

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List three causes of diffuse firm enlargement of the spleen

1. Diffuse granulomatous disease (histoplasmosis)

2. Neoplasms (round cell tumors)

3. Storage disease/amyloidosis

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Important note about lymphoma

Can be diffuse firm OR nodular firm

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Important note about storage disease/amyloidosis

RARE AF

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List differentials for firm nodules in the spleen

-Lymphoid and complex nodular hyperplasia

-Primary OR metastatic neoplasia

-Granulomas/abscesses

-Extramedullary hematopoiesis

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2 bacteria that cause splenic abscesses

1. Rhodococcus equi

2. Trueperella pyogenes

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2 bacteria that cause splenic granulomas

1. Tularemia

2. Mycobacteria

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Nodular firm neoplasia

Primary = lymphoma, histiocytic sarcoma, splenic stromal sarcomas, solid hemangiosarcomas, myelolipomas

Metastatic = sarcomas, carcinomas, malignant round cell tumors

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Cell of origin histiocytic sarcoma

Monocytic/histiocytic origin (dendritic cells and macrophages)

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Important note about histiocytic sarcoma pattern

Can be diffuse firm and nodular firm

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What are common tissues affected by histiocytic sarcoma?

Spleen, lung, liver, skin, articular surface of joints, bone marrow

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What are common breeds affected by histiocytic sarcoma?

-Bernese mountain dogs

-Flat-coated retrievers

-Golden retrievers

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LN/LYMPHATICS SECTION

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Recognize normal architecture and pattern of LNs

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Where do T cells live in the LN?

Paracortex

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Where do histiocytes and macrophages live in the LN?

Medulla

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Where do B cells live in the LN?

Cortex

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Enteric lymphangiectasia/itis in the dog gross findings

Will see the lymphatics and pinpoint dots inside of the mucosa

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Enteric lymphangiectasia/itis in the dog clinical findings

chronic diarrhea, wasting, hypoproteinemia, lymphopenia, hypocalcemia, hypocholesterolemia

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Enteric lymphangiectasia/itis in the dog histo

Dilated lymphatics

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What is the cause/pathogenesis of serosal lesions?

Intestinal lipogranulomatous lymphangitis = accumulations of granulomatous inflammation forming white masses

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Enteric lymphangiectasia VS intestinal lipogranulomatous lymphangitis

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4 causes of chylothorax

o Idiopathic

o Trauma

o CHF

o Chest tumors

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Clin path finding of chylothorax

lymphopenia due to loss of lymphocytes in fluid

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Causes of lymph node atrophy

-Primary immunodeficiency disease

-Lack of antigenic stimulation

-Viral infections

-Cachexia & malnutrition

-Aging

-Radiation

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Viruses that can injure lymphoid tissue

-Parvovirus

-FIV

-BVDV

-Distemper

-Ehrlichia

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Name common species to be affected by Yersinia pestis

Squirrels, prairie dogs, rabbits, wood rats

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How is plague spread?

Bite by infected flea or consumption of infected animal

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Gross findings of plague in cats

Fever, loss of appetite, lethargy, enlarged LNs

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Name three other bacterial causes of lymphadenitis/adenomegaly

-Mycobacterium avium ssp paratuberculosis

-Rhodococcus equi

-Streptococcus equi ssp equi

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Name a fungal cause of lymphadenitis/adenomegaly

Histoplasmosis

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Name two causes of bacterial lymphadenitis in horses

-Streptococcus equi ssp equi (Strangles)

-Rhodococcus equi

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Streptococcus equi ssp equi

-Term for systemic spread = bastard strangles

-Purpura hemorrhagica (type III) from repeated exposure

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Rhodococcus equi

-Foals up to 6 months old causing bronchopneuonia

-50% develop progranulomatous ulcerative enterotyphlocolitis of Peyer's patches

-Pyogranulomatous inflammation with phagocytized bacteria

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3 bacterial causes of bacterial lymphadenitis in cattle or sheep

1. Johne's Disease

2. Bovine Tuberculosis

3. Caseous Lymphadenitis

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Johne's disease cause

mycobacterium avium paratuberculosis

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Johne's disease gross findings

Enteritis and granulomatous lymphadenitis

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Johne's disease stain

Acid fast within macrophages

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Bovine tuberculosis cause

Mycobacterium bovis

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Bovine tuberculosis gross findings

Necrotic and suppurative/abscessed lymph nodes

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Bovine tuberculosis human infection

Raw milk

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Caseous lymphadenitis cause

gram + intracellular bacterium corynebacterium pseudotuberculosis

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Caseous lymphadenitis transmission

enters through skin wounds —> drain to regional LN —> disseminate in lymph and blood