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Lymphoma
neoplasm of lymphocytes arising as a solid tissue mass in organs other than the bone marrow
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Lymphocytic leukemia
- neoplasm od lymphoid cells that originates from bone marrow
- can be found in blood (leukemic) or not (aleukemic)
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Acute myeloid leukemia (AML)
- usually leukocytosis
- undifferentiated blast cells in blood
- >20% nucleated cells are blasts and >50% total nonerythroid cells are nucleated cell pop
- blast cell origin cannot be determined by morphology alone
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Chronic myeloid leukemia
- slowly progresses
- older animals
- clonal neoplastic proliferations of mature granulocytes, monocytes, erythrocytes, or platelets
- leucocytosis
- bone marrow hypercellularity
- blast crisis- transformation to acute myeloid leukemia
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Myelodysplastic syndrome (MDS)
- pre-leukemic condition
- <20% blast cells in bone marrow
- hypercellular bone marrow
- associated with FeLV
- possible leukopenia, anemia, thrombocytopenia
- anemia is nonreg, macrocytic, lack polychromasia, metarubricytes present
- macrocytosis, abnormal nuclear lobulation
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Mast cell neoplasm
- subset of CFU-GEMM
- common in dogs, common in skin (consider malignant)
- cats- skin or visceral (single= bengin, multiple= malignant)
- mast cell leukemia- formed bad in marrow and released into blood- GI common and release histamine
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Histocytic neoplasia
- cell of mac, dendritic, or langerhan cell lineage
- common in dogs
- cutaneous, canine cutaneous, systemic, sarcoma complex
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Canine cutaneous histiocytoma
- unique in young dogs
- neoplasm of dendritic Ag presenting and Langerhans cells
- benign
- solitary
- excision to cure
- spontaeously regress
- cherry red lesion
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cutaneous histiocytosis
- benign
- multiple lesions
- wax and wane
- mostly reactive
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Systemic histiocytosis
- multiple lesions
- involves regional LN
- reactive
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histiocytic sarcoma complex
- solitary
- extends beyond regional LN and involves visceral tissues
- Bernese mountain dogs
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neutrophils in cytology
- not normally present
- short life span (12-24hr)
- non degenerate- none septic mostly
- degenerate- sepsis
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eosinophils in cytology
- not normally present
- casuses- hypersensitivity, allergic response, parasites, mast cell tumor, T cell lymphoma, fungal inf, idiopathic
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macrophages in cytology
- aka- histiocytes
- small numbers normally
- chronic infection
- causes- fungal inf, necrosis, foreign body, complex bac, neoplasia
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epithelioid macrophage
- not normally present
- produce cytokines, Ag presenting
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multinucleated giant cell
- not normally present
- frustrated phagocytosis
- granulomatous and pyogranulomatous
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mast cell
- not normally present
- granules may not stain in Diff- Quik
- cause- hypersensitivity, mast cell tumor
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Lymphocytes
- not normally present
- cause- plasma cell tumor
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suppurative inflammation
- 85% neutrophils
- septic or mycotic?
- degenerate or nondegenerate neutrophils?
- usually acute
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eosinophilic inflammation
- 50% eosinophils
- could be suppurative and eosinophilic inf
- septic or mycotic?
- causes- parasite, hypersensitive, mast cell tumor, T cell lymphoma, allergic rxn, idiopathic
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mixed inflammation
- neutrophils, mononuclear cells, eosinophils, mast cells
- chronicity
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pyogranulomatous inflammation
- neutrophils and macs
- multinucleated giant cells or epithelioid macs
- causes- foreign body, fungi
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granulomatous inflammation
- lacks neutrophils
- multinucleated giant cells
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lymphocytic or lymphoplasmacytic inflammation
inc in small lymphs and plasma cells in non-lymphoid tissue
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RBC in cytology
- contamination- RBCs with platelets
- hemorrhage- erythrophagocytosis, hemosiderophages, hemosiderin
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Basic mechanisms for body cavity effusions
- dec plasma oncotic press
- inc hydrostatic press
- lyph obstruction
- inc vascular permeability
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transudate
- low total protein and low nucleated cell counts
- non-inflammatory- hypoalbuminemia, lymph obstruction, inc blood press
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Modified transudate
- mildly inc nucleated cells and protein
- cause- R sided heart failure, neoplasia, infection (FIP)
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exudate
- high total protein and nucleated cell counts
- mostly neutrophils
- cause- inflammation from sepsis, perforated intestine, neoplasia, necrosis
- suppurative, mixed cell, lymphocytic, eosinophilic?
- septic or mycotic?
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Equine peritoneal fluid
- normal- transudate
- nucleated cell count normally higher
- modified transudate- impaction, gastritis, early GI lesions
- exudate- ruptured gut, intussusception, colitis
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chylous effusion
- causes- leakage secondary to trauma, heart failure, neoplasia, obstruction, idiopathic
- milky white fluid
- lipid will falsely inc TP
- tryglicerides higher in fluid than serum
- cholesterol lower in fluid than serum
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hemorrhagic effusion
- lots of RBCs
- erythrophogocytosis, hemosiderin, hemotoidin
- no inflammation
- no platelets
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Cerebrospinal fluid (CSF)
- clot tube
- microprotein- low
- pandy- est of Ig- none or trace
- cell count- few nucleated, no RBC
- pleocytosis- inc nucleated cells
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pleocytosis
- inc number nucleated cells in CSF
- microprotein usually also increased
- neutrophilic (IVD, immune mediated, FPT), eosinophilic, large mononuclear, mixed cell, lymphocytic
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synovial fluid
- highly viscous from hyaluronic acid
- mucin clot test
- TP and cell count- must add hyaluronidase to dec viscosity
- supurative, mononuclear, or mixed cell inf
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suppurative inflammation of synovial joint
- inc nucleated cell counts- primarily neutrophils
- sepsis- assume if horse
- immune mediated dz- assume if dog
- trauma
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neoplasia in cytology
- monomorphic population
- benign-
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benign cells
- well differentiated
- slow growth
- uniform in size
- blue staining cytoplasm
- uniform N:C ratio
- no mitotic figures
- ddx: hyperplasia
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malignant cells
- mitotic activity
- high cellularity
- abnormal cell type for that area
- monomorphic cells with pleomorphism
- anisocytosis and macrocytosis
- basophilic cytoplasm
- nuclear pleomorphism
- anisokaryosis
- variable N:C ratios
- multinucleation
- nuclear molding
- inc mitotic figures
- abnormal chromatin patterns
- macronucleoli
- multiple nucleoli
- abnormal shaped nucleoli
- anisonucleoliosis
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epithelial tumors
- small, round cells
- highly cellular
- clustering nature
- benign- oma
- malignant- carcinoma
- ex- skin, intestine lining, lung, liver
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mesenchymal tumors
- spindle or round cells
- low to mod cellularity
- not in cohesive sheets
- protein background
- benign- oma
- malignant- sarcoma
- ex- CT, bone, muscle, cartilage
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round cell tumor
- round cells
- high cellularity
- cells do not have cohesion
- cutaneous histiocytoma, lymphoma, cutaneous mast cell tumor, plasma cell tumor, transmissible venereal tumor, histiocytic neoplasia
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cutaneous histiocytoma
- benign
- young dogs
- small button like raised mass
- Langerhan cells
- many lymphocytes present
- spontaneous regression
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lymphoma
- malignant
- normal lymph tissue 90% small lymphocytes
- with lymphoma >50% immature lymphocytes
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cutaneous mast cell tumor
- benign or malignant (tx like malignant)
- cells with purple granules
- eosinophils may be present
- poor granulation= poor prognosis
- not as bad in cats
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plasma cell tumors
- benign or malignant
- cutaneous near footpad
- if in bone marrow- malignant
- flame cells
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transmissible venereal tumor (TVT)
- malignant, but excellent prognosis
- dogs on genitalia or face
- spread by direct contact
- small peripheralized and uniformly sized and shaped clear cytoplasmic vacuoles
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histiocytic neoplasm
- malignant or benign
- spleen, bone marrow, lung, liver
- originate from macs
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malignant melenoma
- neuroectoderm origin
- round, mesenchymal, epithelial
- greenish- black cytoplasm
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basic events in normal clot formation
- vasoconstriction
- platelet adhesion
- conformation change of platelets
- platelet aggregation
- clotting path activation
- fibrin meshwork
- resolution of clot formation thru fibrinolysis
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blood vessel endothelium contents
- anticoagulant- antithrombin, tissue plasminogen activator, tissue factor pathway inhibitor
- procoagulant- prothrombin, vWF, plasminogen activator inhibitor, endothelin
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platelets
- primary hemostasis
- live 7-10 days
- bind to vWF on endothelial collagen in damaged blood vessels
- conformational change enhances binding, expose phospholipids, release thromboxane/Ca/platelet activating factor
- form loose plug
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Thromboxane (TxA2)
- released from platelets
- vasoconstriction
- platelet aggregation
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clotting factor pathway activation
- secondary hemostasis
- named with a roman numeral
- non-activated or resting factor (ex- X, VII)
- activated factors (ex- Xa, VIIa)
- most factors made by liver (except IV, III)
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factor I(a)
fibrinogen (fibrin)
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factor II(a)
prothrombin (thrombin)
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clotting factors that require vit K
II, VII, IX, X, protein C&S
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exception for factor V and VIII
- all other factors have enzymatic activity so thy are not consumed in the reaction to activate the clotting path
- factors V and VIII are consumed so prone to consumption if liver cannot keep up prod
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intrinsic pathway
- XII, XI, IX, VIII
- HMWK and PK
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inactivation of clotting pathway
- tissue factor pathway inhibitor (TFPI)- inactivates VIIa
- antithrombin- inactivates IIa- amplified by heparan
- thrombomodulin- activates protein C which combines with S and inactivates V and VIII
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fibrinolysis
- initially plasminogen activator inhibitor is released
- when healing tissue releases tissue factor plasminogen activator
- fibrin must be present for plasminogen to convert to plasmin
- plasmin breaks down clot
- plasmin is a protease so if free then alpha-2 antiplasmin inactivates it
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quanitative platelet disorders
- thrombocytopenia
- thrombocytosis
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thrombocytopenia
- hemorrhage when platelets are <25,000
- normal bone marrow response is megakaryocytic hyperplasia
- causes- sequestration, consumption (DIC), destruction (IMHA/IMT), hemorrhage, dec production
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thrombocytosis
- reactive- most common, iron deficiency or anemia lead to erythroid hyperplasia and a piggyback megakaryocytic hyperplasia
- physiologic- splenic contraction, transient
- neoplastic- essential thrombocythemia (ET)
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qualitative platelet disorders
- hereditary primary platelet defects
- von Willebrand Disease
- acquired platelet dysfunction
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hereditary primary platelet defects
- glazmann's thrombasthenia- otterhound, great pyrenees
- chediak-higashi syndrome- persian cat, hereford cattle
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von Willebrand Disease
- appears as a platelet defect
- platelet numbers and fxn are normal
- produced and stored in endothelial cells and bound to VIII
- type I- fewer numbers of all sizes, doberman
- type II- loss of high molecular weight multimers, GSP, severe bleeding
- type III- loss of all multimers, scottish terrrier, shetland sheepdog, severe bleeding
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acquired platelet dysfunction
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buccal mucosal bleeding time test (BMT)
- assess formation of platelet plug only
- 2-4 min
- do not do if low platelets
- prolonged= vWD, qualitative platelet defects
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deficiency of XI and XII
- do not cause much bleeding bc alternate path
- XI- cattle
- XII- cats
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deficiency of VII
- minor bleeding prob
- boxer, beagle, malamute
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deficiency of V, IX, X, VIII
- severe bleeding
- boxer, cocker
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vit K deficiency
- V, VII, IX, X
- protein C&S
- cause- rodenticide toxicity, moldy sweet clover
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coagulation test
- Na citrate tube
- fill to proper level
- centrifuge ASAP
- measures time to form clot in tube
- platelets not present
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activated clotting time (ACT)
- grey top
- whole blood
- must be less than 5% of normal (95% dec)- insensitive
- intrinsic and common path
- do not perform with severe thrombocytopenia
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activated partial thromboplastin time (APTT)
- intrinsic and common path
- must be less than 30% of normal (70% dec)
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prothrombin time (PT)
- VII and common path
- best test for vit K deficiency bc VII affected first
- nust be less than 30% of normal (70% dec)
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D-dimer
specific breakdown product of cross linked fibrin and so measuring this substance is a better way to evaluate if fibrinolysis of the clot is occuring
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FDPs
increased= DIC, thrombotic dz, liver dz, hemorrhage
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hypercoagulability
- inc platelet activity
- inc coag factors
- dec natural inhibitors
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antithrombin
- percent activity compared to a normal standard
- hepatic insufficiency, protein losing nephropathy, DIC
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disseminated intravascular coagulation (DIC)
- multifactoral- widespread fibrin formation
- consumption of platelets, coag factors, natural inhibitors, fibrinolytic factors
- results in thrombosis
- ischemia and anoxia leads to acidosis
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underlying mech for DIC
- stagnant blood flow
- endothelial damage
- release of tissue factors
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clinical signs of DIC
- petechia
- ecchymoses
- frank hemorrhage
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diagnosis of DIC
- three of any of the following:
- thrombocytopenia
- prolonged PT/APTT
- inc D-dimer
- dec fibrinogen
- dec antithrombin
- schistocytes
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Enzyme summary
- measurements are based on degree of activity not quantity
- international units per L
- do not have fxn in blood
- dec levels are non-diagnostic
- inc levels= damaged cells, induction, neoplasia, dec clearance, ingestion
- degree of enzyme elevation correlates to the degree of cellular damage (does not mean diffuse)
- 3-5 fold inc is significant
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clinical signs associated with hepatic dz
- lethargy
- dep
- icterus
- bleeding
- vomiting
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lab results associated with liver dz
- anemia, acanthocytes
- hypoproteinemia
- ammonium biurate crystals
- abnormal coagulation profiles
- transudate
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hepatocellular damage
- ALT, AST, GLD, SDH
- near vessels so quick inc in blood
- leakage from ruptured cells
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cholestasis
- LALP
- GGT
- then ALT, AST, GLD, SDH
- intra or extrahepatic
- induction of enzyme activity by press
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hepatic insufficiency
- hypoglycemia/albuminemia
- portosystemic shunt- microhepatica
- down reg of albumin
- chronic liver dz
- inc albumin loss
- horse albumin has long half life
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Alanine transaminase (ALT)
- liver
- half life dog-3d, cat-3.5hr
- inc may result from glucocorticoid or anticonvulsant
- not run in LA
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Aspartate traansaminase (AST)
- mitochondria- liver and skeletal mm
- half life dog-12hr, cat-1.5hr, horse-8d
- not run in SA
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Iditol or sorbitol dehydrogenase (ID, SDH)
- acute injury
- not run in SA
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Alkaline phosphate (ALP)
- intestine, liver, bone
- L-ALP half life dog-3d, cat-6hr
- corticosteroid induced ALP in dogs
- causes for inc= cholestasis (SA), phenobarb, young growing animal, mammary neoplasm, corticosteroid, hepatic lipidosis, hyperthyroidism
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gamma-glutamyl transferase (GGT)
- liver, bile duct, renal
- half life 3d
- causes of inc= corticosteroids, colostrum, cholestasis (SA and horses), biliary neoplasia
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