Clinical Pathology Chapter 6

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Clinical Pathology Chapter 6
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Clinical Pathology Chapter 6
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  1. Where is the site of blood cell production
    Bone MarrowMarrow is present in the medullary cavities of bones
  2. What is extramedullary hematopoesis
    In extreme cases areas such as the liver and spleen can produce blood cells
  3. Where are erythrocytes, granulocytes, monocytes and platelets and some lymphocytes formed
    in the Bone Marrow
  4. Where are most lymphocytes made
    In the lymph nodes
  5. In young animals marrow in all bones is active and highly cellular
    Red Marrow
  6. As animals age, the amount of active marrow in the long bones decreases and is replaced with fat. Yellow Marrow
    Marrow remains active in flat bones (ribs, sternum, pelvis, and skull)
  7. Youngest to adult cell development
    Rubriblasts Rubriblast- prorubicyte-rubricyte- metarubicyte (nucleated Reb Blood Cell)-retiulocyte-RBC (erthrocyte)
  8. Youngest to adult cell development
    Myeloblast Myeloblast- promyelocyte- myelocyte-metamyelocyte-granulocyte (neutrophil, basophil, eosinophil)
  9. Youngest to adult cell development
    Monoblast monoblast- monocyte
  10. Youngest to adult cell development
    Lymphoblast (T or B)Lymphoblast (T or B) - Lymphocyte (T or B) B cells are produced in the Bone marrow. The precursors of T cells are also produced in the bone marrow but leave the bone marrow and mature in the thymus
  11. Youngest to adult cell development Megakaryoblast
    Megakaryoblast- megakaryocyte-multiple platelets
  12. Reasons to examine bone marrow
    Non-regenerative anemia of undetermined cause Abnormal cells are found on the blood smear Culture in cases of osteomyelitis
  13. Define Osteomyelitis
    Inflammation of the bone
  14. Where are the collection sites for bone marrow
    Proximal HumerusProximal femurWing of the ilium
  15. What are the bone marrow collection needles called
    • Rosenthal bone marrow aspiration needle
    • jamshidi needle is used to get bone marrow core for biopsy.
  16. What is the first step in bone marrow inspection
    Perform a naked eye inspection of the slides to select the smear containing the best particles (Marrow Fragments)
  17. Define Normocellular
    Hypocellular
    Hypercellular
    Normocellular- normal amounts and types of cells Hypocellular- containing less than the normal number of cells Hypercellular- containing more than the normal number of cells
  18. What is the second step in bone marrow inspection
    Slide Cellularity: With 10x objective survey the particles whether they are normocellular, hypocellular or hypercellular. In many cases one may just obtain blood (blood tap) or nothing at all (dry tap) When not enough bone marrow fluid is collected in a bone marrow aspiration.Under these conditions the aspirate has to be repeated, or a bone marrow biopsy has to be performed.
  19. What is the Third step in bone marrow inspection
    Myeloid to Erythroid ratio: Use the 10x or 40x objective. The number of large, pale-staining cells with disperced chromatin (ie. myeloic cells) should be compared to the number of dark-staining with clumbed chromatin (i.e (erythroid cells) This is a quick, but reliable method of determining the M:E ratio. Normal ratios vary from 1:1 to 3:1
  20. What is a myloid cell suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cordWhat is erthroid cells Cell that will give rise to erythrocytes
    • Bone Marrow Disfunction can be caused by several things one of which is What are infectious agentsErthlichiosis- Tick bornFeLV -Feline Leukemia VirusFIP Virus- Feline infectious peritonitisBone Marrow Disfunction can be caused by several things one of which is Chemicals and Toxins Chemotherapy and radiationBone Marrow Disfunction can be caused by several things one of which is Immune Mediated diseaseITP- Immune Mediated ThrombocytopeniaIMHA- IMMUNE MEDIATED HEMOLYTIC ANEMIA or “IMHA” (FORMERLY KNOWN AS AUTOIMMUNE HEMOLYTIC ANEMIA or “AIHA”Bone Marrow Disfunction can be caused by several things one of which is Myelophistic DiseaseThe componants of marrow are being "crowded out by abnormal cells. Most often due to neoplasia of one or more of the cells in the normally exist in the marrow.Myeloproliferative disease (cancer)Define Hemostasis Hemostasis is the process the body uses to stop the flow of blood when the vascular system is damaged.There are 3 mechanisms tht help prevent excessive blood loss after vessel rupture. What are theyVascular SpasmsPlatelet FormationClot formation or coagulationWhat are platelets Platelets (thrombocyte) are formed in the bone marrow and are cell fragments derived from megakaryocytes.Function of plateletsto Form the initial plug at the site of hemorrageRelease numerous active chemicals which initiate the clotting processDefine Normocellular HypocellularNormocellular- normal amounts and types of cells Hypocellular- containing less than the normal number of cells Hypercellular- containing more than the normal number of cellsWhat is the third step in bone marrow inspectionMyeloid to Erythroid ratioUse the 10x or 40x objective. The number of large, pale staining cells with dispersed chromatin (myeloid cell) should be compared to the number of dark staining cells with clumped chromatin (ie. erythroid cells). This is a quick, but reliable method of determining the M:E ratio.. Normal ratios very from 1:1 to 3:1What is a myloid cell suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cordWhat is erthroid cells Cell that will give rise to erythrocytesWhat is the fourth and final step in Bone Marrow Inspection Maturation of erythroid and myeloid series: In normal bone marrow 80% of the nucleated series should be rubricytes and metarubricytes. In the myeloid series, 80% of cells should be metamyelocytes, bands, and segmented Neutrophils. Blast cells should be less than 5% of the neutrophils. Blast cells should be less than 5 % of the total. If the greater than 30% of cells are blasts cells, a hemic neoplasia (ie. leukemia) is probably present.Bone Marrow Disfunction can be caused by several things one of which is What are infectious agentsErthlichiosis- Tick bornFeLV -Feline Leukemia VirusFIP Virus- Feline infectious peritonitisBone Marrow Disfunction can be caused by several things one of which is Chemicals and Toxins Chemotherapy and radiationBone Marrow Disfunction can be caused by several things one of which is Immune Mediated diseaseITP- Immune Mediated ThrombocytopeniaIMHA- IMMUNE MEDIATED HEMOLYTIC ANEMIA or “IMHA” (FORMERLY KNOWN AS AUTOIMMUNE HEMOLYTIC ANEMIA or “AIHA”Bone Marrow Disfunction can be caused by several things one of which is Myelophistic DiseaseThe componants of marrow are being "crowded out by abnormal cells. Most often due to neoplasia of one or more of the cells in the normally exist in the marrow.Myeloproliferative disease (cancer)Define Hemostasis Hemostasis is the process the body uses to stop the flow of blood when the vascular system is damaged.There are 3 mechanisms tht help prevent excessive blood loss after vessel rupture. What are theyVascular SpasmsPlatelet FormationClot formation or coagulationWhat are platelets Platelets (thrombocyte) are formed in the bone marrow and are cell fragments derived from megakaryocytes.Function of plateletsto Form the initial plug at the site of hemorrageRelease numerous active chemicals which initiate the clotting process
  21. What is the fourth and final step in Bone Marrow Inspection
    Maturation of erythroid and myeloid series: In normal bone marrow 80% of the nucleated series should be rubricytes and metarubricytes. In the myeloid series, 80% of cells should be metamyelocytes, bands, and segmented Neutrophils. Blast cells should be less than 5% of the neutrophils. Blast cells should be less than 5 % of the total. If the greater than 30% of cells are blasts cells, a hemic neoplasia (ie. leukemia) is probably present.
  22. Bone Marrow Disfunction can be caused by several things one of which is
    • What are infectious agents
    • Erthlichiosis- Tick born
    • FeLV -Feline Leukemia Virus
    • FIP Virus- Feline infectious peritonitisBone
  23. Marrow Disfunction can be caused by several things one of which is
    • Chemicals and Toxins
    • Chemotherapy and radiation Bone Marrow Disfunction can be caused by several things one of which is Immune Mediated diseaseITP- Immune Mediated Thrombocytopenia
    • IMHA- IMMUNE MEDIATED HEMOLYTIC ANEMIA or “IMHA” (FORMERLY KNOWN AS AUTOIMMUNE HEMOLYTIC ANEMIA or “AIHA”Bone Marrow Disfunction can be caused by several things one of which is Myelophistic Disease The componants of marrow are being "crowded out by abnormal cells. Most often due to neoplasia of one or more of the cells in the normally exist in the marrow.Myeloproliferative disease (cancer)
  24. Define Hemostasis
    Hemostasis is the process the body uses to stop the flow of blood when the vascular system is damaged.
  25. There are 3 mechanisms that help prevent excessive blood loss after vessel rupture. What are they
    Vascular SpasmsPlatelet FormationClot formation or coagulation
  26. What are platelets .
    Platelets (thrombocyte) are formed in the bone marrow and are cell fragments derived from megakaryocytes
  27. Function of platelets
    • to Form the initial plug at the site of hemorrage
    • Release numerous active chemicals which initiate the clotting process
  28. Platelets are attracted to expose collagen fibers in broken blood vessels. After attachment they
    degranulate, relaeasing chemicals, which attract other platelest and initiate the clotting process
  29. The clotting process
    • Platelets and or other tissue factors initiate the clotting process.
    • The clotting process is a complex series of enzyme (clotting factors) activations which ultimately leads to the formation of fibrin
  30. The series of activations is called
    • Clotting Cascade
    • Most of these clotting factors are plasma proteins produced in the liver and have both a number and a name.
    • There are two pathways which the clotting cascade can proceed.
  31. What are the two pathways in which the clotting cascase can proceed
    • intrinsic pathway
    • extrinisic pathway
  32. Both the intrinsic and extrinsic pathways merge into a final common pathway.
    The intrinsic system is activated when the endothelial lining of a blood vessel ruptures. If the intrinsic system starts the coagulation process, only factors that are present in (or intrinsic to) plasma are needed to start coagulation.
  33. The extrinsic sytem requires a membrane factor that is not a component of circulating blood.
    The release of tissue thromboplastin (factor III) initiates the extrinsic system.
  34. Clotting factor nomenclature
    • Factor 1 fibrinogen
    • Factor 2- prothrombin
    • Factor 3- Tissue thromboplastin
    • Factor 4- Calcium
  35. Whether the extrinsic or intrinsic system starts the process, coagulation occurs in four stages
    • Stage one- Release of factors (platelet or tissue factors) that begin the clotting process
    • Stage two- Activation of Factor X as calcium and other factors interact
    • Stage 3- Conversion of prothrombin to thrombin
    • Stage 4- Formation of fibrin form fibrinogen
  36. Hemostatic Defects
    Clotting factors
    • Problems with clotting factors are generally hereditary; a factor is deficient or does not work properly
    • Hemophilia A - Factor VIII antihemophilic globulin deficiency
    • Hemophilia B- Factor IX Christmas factor deficiency
    • Hemophilia C - Factor XI plasma thrommoplastin antecedent
    • Type 3 Von Willebrands disease
  37. Production of clotting factors may ne inhibited by liver disease ( liver producers enzymes and clotting factors)
    Certain drugs can interfere with the function of certain factors
    Many rat poisons (like Warfarin) kill by causing excessive bleeding. These drugs interfere with the production of Vitamin K which is necessary for the liver production and activation of clotting factors2, 7, 9, and 10.
  38. What is the most common hereditary canine bleeding disorder
    Von Willebrand Disease
  39. What is the cause of Von Willebrand Disease
    Lack of function of von willebrand factor, which plays a role by supporting platelet adhesion at sites of vessel injury.
  40. What are the breeds that might have Von Willebrand disease
    Dobermans, akita, cockers, german shepards, irish wolfhounds, dachshund
  41. Clinical signs of Von Willebrand
    Mucous membrane hemorrage, bruising, epistazis, (nose bleed) Bleeding from the teeth, prolonged bleeding from surgery site.
  42. Diagnosis of von Willebrand
    • Prolonged BMBT>5 minutes
    • vWF Antigen assays (Elisa test) <50%
  43. Treatment for Von Willbrand
    • Plasma ctyoprecipitate (has von willebrand in it)
    • Desmopressin
  44. Hemostatic Defects of Von Willbrand

    Thrombocytopenia and Platelet dysfunction
    Platelets problems may be categorized as
    Quantitative and qualitative
  45. Define Quantitative
    Decreased numbers of platelets is referred to as thrombocytopenia
  46. Causes of thrombocytopenia are numerous including
    • Immune mediated thrombocytopenia
    • Autoantibodies attack platelets

    • DIC- Platelets are consumed(used up) as millions of tiny clots are formed throughout the body.
    • Infectious- Infectious agents which attack platelets or platelet precursors leading to thrombocytopenia (Ehrlichia) tick borne
    • Conditions affecting bone marrow production
  47. Qualitative
    • Platelets numbers are adequate but they do not function properly
    • Type 2 von willebrands disease is a hereditary defect where plateles don't adhere properly
    • Drugs: Multiple drugs inhibit platelet functions
    • Aspirin
    • NSAIDS
  48. Coagulation test
    • coagulation test are used to diagnosis vavious bleeding disorders
    • Different coagulation test are designed to evaluate either the intrinsic pathway, the extrinisic pathway or platelet function.

    • Depending on the test, the sample ma be whole blood or plasma.
    • When anticoagulation of the blood sample is necessary, sodium citrate (lavender top) is the anticoagulant of choice.
  49. Define Activatiing clotting time ACT
    • ACT is a common veterinary office test.
    • ACT procedure uses diatomaceous earth prefilled tubes as an activating agent, shortening the normal clotting time.
    • Whole blood is drawn with a plastic syringe and placed in a pre-warmed ACT tube. The tube is inverted 5 times to mix (minimum 2 mLs)
    • The tube is incubated for 1 minute then removed, tilted, and examined at 5 second intervals for signs of clotting. The endpoint is the first evidence of clotting.
    • Normal values are about 60-90 seconds
    • Severe thrombocytopenia (fewer than 10,000 Platelets/uL) and abnormalities associated with the intrinsic coagulation cascade prolong the ACT
  50. Bleeding Time
    • Bleeding Time is prolonged in platelet defects (qualitative or quantitative) and von Willebrand's disease
    • (Buccal mucosal Bleeding time- BMBT)
  51. Procedure
    • A site devoid of hair (such as the nose or inner lip ) is cleaned and punctured with a small lancer or scapel, and timing started.
    • Blood is blotted away at 30 seconds intervals with filter paper
    • The endpoint is when blood no longer appears from the pucture site.
    • Normal bleeding time in most domestic animals is 1 to 3 minutes
    • More sophisticated platelet evaluation for platelet aggregation and adhesion can be carried out at commercial labs.
  52. Activated Partial Thromboplastin Time
    • APTT is not done a local vet hospitals- SA2000
    • This test requires the submission of citrated plasma
    • The lab adds factor XII and calcium, and the precise time of fibrin formation is measured with a fibrometer.
    • Normal range for domestic animals is 14- 20 seconds
    • Test evaluates the intrinsic cascade
  53. Prothrombin Time
    • PT is not done at a local vet hospital - SA2000
    • This test requires the submission of citrated plasma
    • The lab adds tissue thromboplastic-calcium mixture, and the precise time of fibrin formation is measured with a fibrometer.
    • Normal range for dogs 7- 10 seconds
    • Test evaluates the extrinsic cascade, independent of platelet function
    • Prolonged PT may be assaociated with severe liver disease, DIC or hereditary defects in clotting factors. Test is also sensitive to vitamin K antagonists such as warfarin
  54. PIVKA- Protein induced by Vitamin K adsence
    Rat Poisoning
    • When Vitamin K is low, precursor proteins of factors II, VII, IX, X build up and can be detected by the PIVKA test.
    • PIVKAdetermines rodenticide toxicity form hemophilia.
    • PIKVA increases with rodenticide toxicity
    • PIVKA increase within 6 hours of poison ingestion, where as PT rises take 24- 48 hours.
  55. D-Dimer and Fibrin Degradation Factor (FDP)
    • Both product are formed as clots are broken down and degraded
    • Primarily used to determine DIC (overconsumption of
    • High levels of D_Dimer and FDP are seen with DIC states.
    • Hemangiosarcoma
    • Trauma
    • Liver Failure

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