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Altered Hematologic Function part 2 1. Alterations in Leukocytes and Blood Coagulation 2.

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Presentation on theme: "Altered Hematologic Function part 2 1. Alterations in Leukocytes and Blood Coagulation 2."— Presentation transcript:

1 Altered Hematologic Function part 2 1

2 Alterations in Leukocytes and Blood Coagulation 2

3 Leukocytes White blood cells White blood cells Defend body through: Defend body through: – the inflammatory process – phagocytosis – removal of cell debris – immune reactions 3

4 White Blood Cell Types: Granulocytes and Agranulocytes Granulocytes –visible granules in the cytoplasm. Granulocytes –visible granules in the cytoplasm. Granules contain: Granules contain: –Enzymes –Other biochemicals that serve as signals and mediators of the inflammatory response 4

5 Granulocyte cell types: Neutrophils – phagocytes Neutrophils – phagocytes Eosinophils – red granules, associated with allergic response and parasitic worms Eosinophils – red granules, associated with allergic response and parasitic worms Basophils – deep blue granules - Release heparin, histamine and serotonin Basophils – deep blue granules - Release heparin, histamine and serotonin 5

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9 Agranulocytes Granules too small to be visible Granules too small to be visible Monocytes – become macrophages Monocytes – become macrophages Lymphocytes – B cells and T cells = immune functions Lymphocytes – B cells and T cells = immune functions 9

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12 WBC’s originate in red bone marrow from stem cells. WBC’s originate in red bone marrow from stem cells. Granulocytes mature in the marrow and have a lifespan of hours to days Granulocytes mature in the marrow and have a lifespan of hours to days Agranulocytes finish maturing in blood, or in other locations. Monocytes live about months, lymphocytes for years. Agranulocytes finish maturing in blood, or in other locations. Monocytes live about months, lymphocytes for years. 12

13 Types of stem cells: Types of stem cells: –Pluripotent, any germ layers –Multipotent, somewhat limited, diff type of blood cells –Committed progenitor cells Multipotent blood cells: Multipotent blood cells: –Common lymphoid –Common myeloid Committed stem cell makes specific blood cells – stimulated by erythropoietin, thrombopoietin, granulocyte-mononcyte Committed stem cell makes specific blood cells – stimulated by erythropoietin, thrombopoietin, granulocyte-mononcyte 13

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16 Production of WBC’s increases in response to : Production of WBC’s increases in response to : –Infection –Presence of steroids –Decreased reserve of leukocyte pool in bone marrow 16

17 WBC Abnormalities Leukocytosis – increased numbers of WBC’s Leukocytosis – increased numbers of WBC’s –May be a normal protective response to physiological stressors –Or may signify a disease state – a malignancy or hematologic disorder Leukopenia – decreased numbers of WBC’s – this is never normal Leukopenia – decreased numbers of WBC’s – this is never normal –Increases the risk of infections. –Agranulocytosis = granulocytopenia 17

18 Leukeopenia may be due to: Radiation Radiation Anaphylactic shock Anaphylactic shock Autoimmune disease Autoimmune disease Chemotherapeutic agents Chemotherapeutic agents Idiosyncratic drug reactions Idiosyncratic drug reactions Splenomegaly Splenomegaly infections infections 18

19 Mononucleosis Mononucleosis, or mono, is often spread by saliva and close contact. It is known as "the kissing disease," and occurs most often in those age 15 to 17. However, the infection may develop at any age Mononucleosis, or mono, is often spread by saliva and close contact. It is known as "the kissing disease," and occurs most often in those age 15 to 17. However, the infection may develop at any age 19

20 Mononucleosis Self-limiting lymphoproliferative disorder caused by the Epstein-Barr Virus Self-limiting lymphoproliferative disorder caused by the Epstein-Barr Virus Infects 90% of people Infects 90% of people Incorporates into DNA of B cells causing production of antibodies Incorporates into DNA of B cells causing production of antibodies Tc Cells are produced to limit numbers of infected B cells, accounts for increased numbers of lymphocytes. Tc Cells are produced to limit numbers of infected B cells, accounts for increased numbers of lymphocytes. 20

21 Mononucleosis Mono may begin slowly with fatigue, a general ill feeling, headache, and sore throat. Mono may begin slowly with fatigue, a general ill feeling, headache, and sore throat. 21

22 Symptoms of mononucleosis –Fever –Drowsiness –General discomfort, uneasiness, or ill feeling –Loss of appetite –Muscle aches or stiffness –Rash –Sore throat –Swollen lymph nodes, especially in the neck and armpit –Swollen spleen 22

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25 Treatment The goal of treatment is to relieve symptoms. Medicines such as steroids (prednisone) and antivirals (such as acyclovir) have little or no benefit. The goal of treatment is to relieve symptoms. Medicines such as steroids (prednisone) and antivirals (such as acyclovir) have little or no benefit. To relieve typical symptoms: To relieve typical symptoms: Drink plenty of fluids. Drink plenty of fluids. Gargle with warm salt water to ease a sore throat. Gargle with warm salt water to ease a sore throat. Get plenty of rest. Get plenty of rest. Take acetaminophen or ibuprofen for pain and fever. Take acetaminophen or ibuprofen for pain and fever. Avoid contact sports while the spleen is swollen (to prevent it from rupturing). Avoid contact sports while the spleen is swollen (to prevent it from rupturing). 25

26 Leukemia A malignant disorder in which the blood- forming organs lose control over cell division, causing an accumulation of dysfunctional blood cells. A malignant disorder in which the blood- forming organs lose control over cell division, causing an accumulation of dysfunctional blood cells. Uncontrolled proliferation of non- functional leukocytes crowds out normal cells from the bone marrow and decreases production of normal cells. Uncontrolled proliferation of non- functional leukocytes crowds out normal cells from the bone marrow and decreases production of normal cells. 26

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28 Cause appears to be a genetic predisposition plus exposure to risk factors such as: Cause appears to be a genetic predisposition plus exposure to risk factors such as: –Some disorders of the bone marrow and other organs that can progress to acute leukemias –Some viruses –Ionizing radiation in large doses –Drugs –Down syndrome and other congenital disorders 28

29 Classification Leukemias are classified as: Leukemias are classified as: –acute or chronic –Myeloid or lymphoid 29

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31 Acute Leukemias Characteristics: Characteristics: –Abrupt onset –Rapid progression –Severe symptoms –Histological examination shows increased numbers of immature blood cells Survival rate- Survival rate- –Overall for acute leukemias the 5 year survival rate is about 38 %, but certain types have increased survival rates due to advances in chemotherapy. 31

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34 Clinical manifestations Signs and symptoms : Signs and symptoms : –Fatigue –Bleeding –Fever –Anorexia and weight loss –Liver and spleen enlargement Abdominal pain and tenderness – also breast tenderness –Pain in bones 34

35 Neurologic effects are common: Neurologic effects are common: –Headache –Vomiting –Papilledema – swelling of the optic nerve head – a sign of increased intracranial pressure –Facial palsy –Visual and auditory disturbances –Meningeal irritation 35

36 Early detection is difficult because it is often confused with other conditions. Early detection is difficult because it is often confused with other conditions. Diagnosis is made through blood tests and examination of the bone marrow. Diagnosis is made through blood tests and examination of the bone marrow. 36

37 Treatment Chemotherapy Chemotherapy Blood transfusions and antimicrobial, antifungal and antiviral medications Blood transfusions and antimicrobial, antifungal and antiviral medications Bone marrow transplants Bone marrow transplants 37

38 Chronic Leukemias Characteristics: Characteristics: –Predominant cell is mature but doesn’t function normally –Gradual onset –Relatively longer survival time 38

39 The two main types of chronic leukemia are myeloblastic and lymphocytic. The two main types of chronic leukemia are myeloblastic and lymphocytic. Chronic leukemia accounts for the majority of cases in adults. Chronic leukemia accounts for the majority of cases in adults. Incidence increases significantly after 40 years of age. Incidence increases significantly after 40 years of age. 39

40 Course of disease Chronic phase of variable length (4years) Chronic phase of variable length (4years) Short accelerated phase (6-12 months) Short accelerated phase (6-12 months) Terminal blast crisis phase (3 months) Terminal blast crisis phase (3 months) 40

41 Progress slowly and insidiously. Progress slowly and insidiously. Initial symptoms are splenomegaly, extreme fatigue, weight loss, night sweats and low grade fever. Initial symptoms are splenomegaly, extreme fatigue, weight loss, night sweats and low grade fever. Chronic lymphocytic leukemia involves predominantly B cells; only rarely are T lymphocytes involved. Chronic lymphocytic leukemia involves predominantly B cells; only rarely are T lymphocytes involved. –Programmed cell death of these cells does not take place as it would normally. –These old cells do not produce antibodies effectively –Other blood cell types decrease –Infiltration of liver, spleen, lymph nodes and salivary glands. 41

42 Treatment Chemotherapy Chemotherapy Monoclonal antibodies Monoclonal antibodies Bone marrow transplant Bone marrow transplant Non-myeloablative transplant – “graft- vs.-leukemia” effect, i.e. graft can potentially destroy leukemia Non-myeloablative transplant – “graft- vs.-leukemia” effect, i.e. graft can potentially destroy leukemia 42

43 Multiple Myeloma Cancer of plasma cells Cancer of plasma cells Osteolytic bone lesions Osteolytic bone lesions Light chains can be toxic to kidneys Light chains can be toxic to kidneys Replacement of bone marrow and stimulation of osteoclasts Replacement of bone marrow and stimulation of osteoclasts fractures, hypercalcemia, plasmacytomas, heart failure and neuropathy fractures, hypercalcemia, plasmacytomas, heart failure and neuropathy Chemotherapy, bone marrow transplant Chemotherapy, bone marrow transplant 43

44 Lymphomas These affect the secondary lymph tissue – lymph nodes, spleen, tonsils, intestinal lymphatic tissue. These may be thought of more as a solid tumor, since it occurs in solid tissue as opposed to the blood. These affect the secondary lymph tissue – lymph nodes, spleen, tonsils, intestinal lymphatic tissue. These may be thought of more as a solid tumor, since it occurs in solid tissue as opposed to the blood. Two types: Two types: –Hodgkin’s Lymphoma (Disease) and –Non-Hodgkin’s Lymphoma 44

45 Hodgkin’s Lymphoma Distinguished from other lymphomas by the presence of Reed-Sternberg (RS) Distinguished from other lymphomas by the presence of Reed-Sternberg (RS) Begins in a single node and spreads – cancerous transformation of lymphocytes and their precursors. Begins in a single node and spreads – cancerous transformation of lymphocytes and their precursors. Cause is believed to be genetic susceptibility and infection with the Epstein-Barr virus. Cause is believed to be genetic susceptibility and infection with the Epstein-Barr virus. Other – tonsillectomy or appendectomy, wood working Other – tonsillectomy or appendectomy, wood working 45

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47 Clinical Manifestations Painless swelling or lump in the neck Painless swelling or lump in the neck Asymptomatic mass in the mediastinum found on x-ray Asymptomatic mass in the mediastinum found on x-ray Intermittent fever, night sweats Intermittent fever, night sweats Weakness, weight loss Weakness, weight loss Obstruction / pressure caused by swelling lymph nodes can lead to secondary involvement of other organs. Obstruction / pressure caused by swelling lymph nodes can lead to secondary involvement of other organs. Anemia, elevated sedimenation rate, leukocytosis, and eosinophilia Anemia, elevated sedimenation rate, leukocytosis, and eosinophilia 47

48 Treatment Treatment: Treatment: –Chemotherapy –Radiation –Prognosis good with early treatment, but early detection is difficult –The five year survival rate is 83%. 48

49 Non-Hodgkin’s Lymphoma This is a generic term for a wide spectrum of disorders that cause a malignancy of the lymphoid system This is a generic term for a wide spectrum of disorders that cause a malignancy of the lymphoid system Causes may be viral infections, immunosuppression, radiation, chemicals, and Helicobacter pylori. Causes may be viral infections, immunosuppression, radiation, chemicals, and Helicobacter pylori. 49

50 The lymphoma arises from a single cell that has alterations in its DNA. The lymphoma arises from a single cell that has alterations in its DNA. Clinical manifestations: Clinical manifestations: –Localized or generalized lymphadenopathy –Nasopharynx, GI tract, bone, thyroid, testes may be involved. 50

51 With only involvement of the lymph nodes survival rate is good With only involvement of the lymph nodes survival rate is good Individuals with diffuse disease do not live as long. Individuals with diffuse disease do not live as long. Treatment bone marrow transplant – or autologous (from the same individual) stem cell transplant Treatment bone marrow transplant – or autologous (from the same individual) stem cell transplant 51

52 Thrombocytes - platelets Characteristics – produced by the fragmentation of megakaryocytes – so are cell fragments Characteristics – produced by the fragmentation of megakaryocytes – so are cell fragments Life span is about 3 days Life span is about 3 days Many are held in the spleen Many are held in the spleen 52

53 Coagulation or Hemostasis Soluble proteins (fibrinogen) are converted into insoluble protein threads Soluble proteins (fibrinogen) are converted into insoluble protein threads Many proteins and factors are part of the clotting cascade, including calcium. Many proteins and factors are part of the clotting cascade, including calcium. 53

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56 Terminology in bleeding disorders Petechiae- pinpoint hemorrhage Petechiae- pinpoint hemorrhage

57 Terminology in bleeding disorders Purpura – larger, less regular Purpura – larger, less regular

58 Terminology in bleeding disorders Ecchymoses – over 2 cm – bruise Ecchymoses – over 2 cm – bruise

59 Terminology in bleeding disorders Hematoma – blood trapped in soft tissue Hematoma – blood trapped in soft tissue

60 Disorders of platelets Thrombocytopenia – decreased numbers of platelets (below 100,000/mm 3 ) Thrombocytopenia – decreased numbers of platelets (below 100,000/mm 3 ) Can lead to spontaneous bleeding, if low enough, and can be fatal if bleeding occurs in the G.I. Tract, respiratory system or central nervous system. Can lead to spontaneous bleeding, if low enough, and can be fatal if bleeding occurs in the G.I. Tract, respiratory system or central nervous system. 60

61 Can be congenital or acquired; acquired is more common. Can be congenital or acquired; acquired is more common. Seen with: Seen with: –Generalized bone marrow suppression –Acute viral infection –Nutritional deficiencies of B 12, folic acid and iron –Bone marrow transplant –drugs, especially heparin, and toxins, thiazide diuretics, gold, ethanol… –Immune reactions 61

62 Heparin induced thrombocytopenia is an immune mediated reaction (IgG) that causes platelet aggregation and decreased platelet counts 5 – 10 days after heparin administration in 5 – 15 % of individuals. Can cause thrombosis and emboli. Heparin induced thrombocytopenia is an immune mediated reaction (IgG) that causes platelet aggregation and decreased platelet counts 5 – 10 days after heparin administration in 5 – 15 % of individuals. Can cause thrombosis and emboli. 62

63 Thrombocythemia This is an increased number of platelets. This is an increased number of platelets. If the platelet count rises high enough ( over 1 million/mm 3 ), can get intravascular clot formation or hemorrhage. If the platelet count rises high enough ( over 1 million/mm 3 ), can get intravascular clot formation or hemorrhage. Can be primary thrombocytothemia – cause unknown, or Can be primary thrombocytothemia – cause unknown, or Secondary thrombocytothemia – occurs after splenectomy when platelets that would normally be stored in the spleen remain in blood. Secondary thrombocytothemia – occurs after splenectomy when platelets that would normally be stored in the spleen remain in blood. –Also due to rheumatoid arthritis and cancers. 63

64 Disorders of Coagulation Clotting factor disorders prevent clot formation. Clotting factor disorders prevent clot formation. May be genetic: May be genetic: –Hemophilia and Von Willebrand’s– genetic absence or malfunction of one of the clotting factors Or acquired - usually due to deficient production of clotting factors by the liver: Or acquired - usually due to deficient production of clotting factors by the liver: –Liver disease –Dietary deficiency of vitamin K 64

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