Patho unit 3 ch20&21

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  1. Imbalances of Erythropoiesis
    • Anemia
    • Poycythemia
  2. Anemia
    • Insufficient RBCs or a decrease in the quality or quantity of hemoglobin
    •   -Low iron intake, hemolysis, autoimmune disease, lack of production in the bone marrow
    • Typical symptoms: Fatigue, weakness, dispnea, and pallor(pail or white)
  3. How are Anemias classified?
    • according to etiology (origin) and morphology (how they look)
    • Etiologies: Fe++ deficiency anemia, folate/B12 deficiency, Hemorrhagic anemia, anemia of chronic disease (ACD), hemolytic anemia
    • Morphologys:
    • volume:
    •   -microcytic- small white blood cells
    •   -Macrocytic- large white blood cells
    •   -Normocytic -normal whit blood cells 
    • Chromasia (color):
    •   -hypocromic
    •   -normochromic
  4. Microcytic-Hypochromic Anemia
    • Pale, small red blood cells
    • usually Fe++ deficiency anemia
  5. Macrocytic-Normochromic
    • Large cells
    • Usually folic acid or vitamin B12 deficiency anemia
  6. Normocytic-Normochromic
    • RBCs are normal size and normal hemoglobin content
    • Usually caused by hemorrhage or hemolysis
  7. typesof Normocytic-Normochromic Anemias:
    Hemolytic anemia
    • Anemia due to red cell lysis
    • Fragile cells, infections, drugs, autoimmunity, circulating antibodies
    • Symptoms: enlarged spleen and jaundice (the liver is not doing its job
  8. types of Normocytic-Normochromic Anemias:
    Hemorrhagic anemia (leaking blood)
    • Anemia due t blood loss- bleeding out
    • Surgery or trauma
    • Symptoms: shock and acidosis (poor tissue oxidation- leads to accumulation of lactic acid)
  9. typesof Normocytic-Normochromic Anemias:
    Anemia of Chronic Disease (ACD)
    Bacterial toxins, cyokines from WBCs, suppression progenitor cells-usually mild
  10. typesof Normocytic-Normochromic Anemias:
    Aplastic Anemia
    • Bone marrow hypo- or aplasia
    • Causes: acquired due to drugs (chemotheropy), viruses, genetics, and neoplasia
    • Symptoms: peechiae, bleeding, infection, pancytopenia (no cells)
  11. Macrocytic-Normochromic:
    Pernicious anemia
    • Intrinsic Factor (IF) deficiency leads to insufficient absorption of vitamin B12 which is necessary for developing RBCs
    • Autoimmunity - autoantibody to gastric parietal cells
    • Syptoms: digestive symptoms, glossitis, peripheral neuropathy (demyelination)- tingling in the extremities.
    • Treatment: replace B12
  12. Macrocytic-Normochromic:
    Folic Acid Deficiency
    • Dietary deficiency inhibits DNA synthesis
    • Alcoholics and the malnourished are hat high risk
    • Symptoms similar to pernicious anemia, but no neurological symptoms
    • Treatment: replacement therapy
  13. Microcytic-Hypochromic Anemia:
    Sideroblastic anemia
    • Dysfunctional iron uptake by erythrolasts producing siderblasts and resulting in decreases synthesis of heme
    • Causes: lead, ethanol, other drugs
    • Symptoms: hepatosphenomegaly , hemochromatosis- Excess storage of iron in the liver, skin, pancreas, heart joints and testes, leading to abnormal pain, weakness, lethargy, and weight loss
  14. Microcytic-Hypochromic Anemia:
    Iron deficiency Anemia
    • Most common cause is due to excessive bleeding and/or poor diet
    • High risk: Pregnant women, adolescents, children, elderly, or anyone with chronic blood loss
  15. What are the signs and symptoms of Iron-Deficiency Anemia?
    • Fatigue, weakness, and shortness of breath
    • Pale earlobes, palms, and conjunctivae
    • Spoon-shaped nails, sore tongue, dryness of the epithelium in the corners of the mouth
  16. Nutritional Requirements for the Development of RBCs
    see table on page 120
  17. Polycythemia
    • Excessively large numbers of RBCs in the blood. (Relative and absolute)
    • -Pathological effects: increased blood viscosity promotes clotting (hypercoagulation) and poor oxygenation is distal tissues
    • -Symptoms: Red color of the face, hands, feet, ears, and mucous membranes. High blood pressure, engorgement of retinal and sublingual veins, and hepatosplenomegaly
    • -Treatment: therapeutic phlebotomy ("bloodletting")
  18. Polycythemia Vera
    • Primary polycythemia because it is not due to another diagnosis 
    • Rare, non-malignant proliferative abnormality of the bone marrow.(it can affect WBCs and platelets
    • High hematocrit 70-80%
    • Tends to occur in men age 40-60 of Jewish or European descent
  19. Secondary Polycythemia (Absolute polycythemia)
    • This is common becuase it is aPhysiologic response to hypoxia
    • -Hypoxic conditions: chronic obstructive pulmonary disease (COPD), high altitude, smoking, sleep apnea
  20. Treatment of Poycythemia
    • Reduction of read cells and blood volume achieved by performing a therapeutic phlebotomy (blood letting), which helps prevent the hyperviscosity and thrombus formation
    • Treat the cause of the hypoxia and the number of red blood cells will decrease
  21. Neutrophilia
    • evident in the first stags of and infection or inflammation
    • If the need for neutrophils increases beyond the supply, immature neutrophils (band neutrophils, or just bands) are released into the blood
    • this premature release is detected in the manual WBC differential and is termed a "shift to the left"
  22. Neutropenia
    • All etiologies of neutropenia represent severe disease!
    •   -Prolonged severe infection
    •     -depletes cellular numbers
    •   -Decreased Production
    •     -Starvation, aplastic bone marrow, chemotherapy
    •   -Reduced Survival
    •     -Autoimmune disease: lupus and rheumatoid arthritis
  23. Eosinophilia
    • Alterations of Eosinophils- begin to lose their granules
    • -Increased in allergic disorders: asthma, hay fever, drug reactions
    • -Increased in parasitic invasions
  24. Monocytosis
    • Alterations of Monocytes-tomany monocytes
    • Monocytes are needed to phagocytose organisms and debris
    • Measurement in blood has poor correlation with disease
    • Usually occurs with neutropenia in later stages of infections
  25. Lymphocytosis
    Increase in lymphocytes in acute viral infections, malignancies (lymphocytic leukemias)
  26. Lymphocytopenia
    • Decrease in lymphocytes
    • Immune deficiencies, drug destruction, viral destruction (AIDS)
  27. Infectious Mononucleosis
    • Acute, self-limiting infection characterized by fever, sore throat, lymphadenopathy, and hepatosplenomegaly
    • -Caused by Epstein-Barr virus (EBV)
    • -Transmitted through saliva
    • -Affects B cells
    • most often occurs in the ages of 10-35
    • Diagnostic test: monospot-aggluation test for presence of heterophilic antibodiesHigh lymphocytes, high WBCAtypical lymphocytes
  28. Leukemias
    • WBC cancer
    • -Malignant disorder of blood-forming cells and blood-forming organs
    • -Uncontrolled proliferation of white blood cells

    Classified by:

    • speed of onset
    •   -acute- rapid
    •   -chronic- gradual
    • Predominant cell type
    •   -myeloid- come from the bone marrow, anything that is not a lymphocyte
    •   -lymphoid- Lymphocytes
  29. Acute leukemia
    • -Undifferentiated or immature cells, usually "blasts" (in blood and bone marrow)
    • -Sudden onset of symptoms
    • -Acute myeloid leukemia (AML) and Acute Lymphoid Leukemia (ALL)
  30. Chronic leukemia
    • -Predominant cells are well-differentiated and easily recognized...but they do not function normally
    • -Gradual onset with longer survival times
    • -Chronic myeloid leukemia (CML) and Chronic Lymphoid Leukemia (CLL)
  31. Signs and symptoms of Leukemias
    • Asymptomatic (19%)
    • Spenomegaly- enlarged spleen
    • Infections
    • Night sweats
    • Fatigue
    • Weight loss
    • Anemia- red cells are getting crowded out 
    • Bleeding- platelet count low due to large cells being crowded out of the bone marrow
  32. Leukemias in adults
    • Acute myeloblastic (myelocytic)(AML)
    • Chronic Lymphocytic (CLL) most common
  33. Leukemia in children
    Acute lymphoblastic (lymphocytic)leukemia (ALL) is the most common
  34. AML (Acute Myelocytic Leukemia)
    • -Acute onset
    • -Myeloblasts
    • -Still has poor survival rate
    • -Mostly affects adults
  35. CML (Chronic Myeloid Leukemia)
    • -Gradual onset
    • -Most demonstrate the Philadelphia chromosome (t9:22)
    • -Low survival rate
  36. ALL (Acute Lymphocytic Leukemia)
    • -Acute onset
    • -B and T cells
    • -Lymphoblasts-Mostly affects children
    • -85% cure rate
  37. CLL (Chronic Lymphocytic Leukemia)
    • -Chronic with lengthy survival
    • -Primarily a diagnosis of the elderly
    • -Usually B cells
  38. Multiple Myeloma
    • -Cancer of Plasma cell (B cell) of the bone marrow
    • -Usually occurs in people over 50
    • -Enzymes that cause osteoclastic activity
    • -destruction of bone
    • -Bence-Jones protein- light chains of the immunoglobulins
    • -high plasma protein level causes hyperviscosity of the blood
    • see p.125
  39. Lymphomas
    • Proliferation of lymphocytes and their precursors on lymphoid tissues
    • The major types :
    •   -Hodgkin's disease (lymphoma)
    •   -Non-Hodgkin's lymphoma
    •     -Many divers types
  40. Hodgkin Disease (Lymphoma)
    • -Characterized by the presence of Reed-Sternberg cells in the lymph nodes
    • -Usually localized- single lymph nodes or chain of nodes
    • -High survival rate
    • -night sweats, fever, weight loss, pruritis (itching)
    • Treatment with radiation and chemotherapy
  41. Non-Hodgkin Lymphomas
    • -No Reed-Sternberg cells
    • -Disseminated (Multiple node and organ involvement)
    • -not localized (spreads)
    • -Poor survival rate
  42. Platelet Disorders
    • Disorders of platelet numbers
    •   -Thombocythemia-to many platelets
    •   -thrombocytopenia- not enough platelets
    • Disorders of platelet function
    •   -Adhesion, aggregation, and secretion
    • Alterations of platelets and soluble coagulation factors affect hemostasis
    •   -can prevent it from occurring or can cause it to happen when it is not needed
  43. Thrombocythemia
    Increased numbers of platelets
  44. Thrombocytopenia
    • -Not enough platelets or they don't function correctly
    • -Platelets under 100,000/mm^3-Cause: hypersplenism, aplastic bone marrow, autoimmune disease, hypothermia, viral or bacterial infections
  45. Essential (Primary) Thrombocythemia
    • -Platelets over 600,000/mm^3
    • -More common in 50-60s
    • -myeloproliferative disorder of stem cells in which platelets are produced in excess
    • -risk of microvasculature thrombosis- clots in the vasculature that block blood supply to organs
  46. Disorders in Platelet Function
    • Platelet number can be normal, yet not function correctly.
    • Demonstrated by a normal platelet count, but an increased bleeding time (BT)
    • Symptoms: Petichiae, mucosal bleeding, and gingival bleeding
    • Two types : Acquired and congenital
  47. Disorders in Platelet Function:
    • Drugs: aspirin and NSAIDs
    • systemic conditions: renal failure and autoimmune diseases like thrombotic thrombocytopenic purpura (TTP)
    • Hematologic alterations: Leukemias
  48. Disorders in Platelet Function:
    Disorders of platelet adhesion, aggregation, secretion, and procoagulant activity
  49. Alteration of Coagulation cascade
    • Administaration of the drug Warfarin (coumadin) causes temporary, reversible vitamin K deficiency (anti coagulant
    •   -Interferes with the synthesis of vitamin k- dependent clotting factors
    •    -II,VII, IX, X
  50. Disseminated Intravascular Coagulation (DIC)
    • -Acquired, deadly and fairly common coagulation disorder
    • -Excessive utilization of clotting factors: caused by anything that can activate widespread coagulation (Infection, inflammation, damaged tissue)
  51. DIC: Activation of Intrinsic (Contact) Pathway
    • activated by something within the blood
    • Gram-negative sepsis (toxins secreted by bacteria), hypoxia, low blood flow rates
  52. DIC: Activation of Extrinsic (Tissue) Pathway
    • activated by damage to tissue
    • Gram-positive toxins, burn injuries, infarctions, surgeries, obstetric accidents, and malignancies
  53. DIC: Activation of Common Pathway (factor X)
    • Activation by substances that enter the bloodstream (enzymes, snake venom)
    • see other DIC slides on p.129
  54. Hemolytic Disease of the Newborn
    Two main causes: ABO incompatibility (most common but mild), Rh factor incompatibility (life threatening)
  55. Hemolytic Disease of the Newborn:
    ABO incompatability
    • In 19-20% of pregnancies, there is a difference in the fetal and maternal blood types
    • Only 1 in 10 result in HDN
    • More mild because A and B antigens are poorly developed at birth, and A and B antibodies in plasma typically don't cross the placenta
  56. Hemolytic Disease of the Newborn (HDN):
    Rh factor incompatability
    • Occurs when maternal anti-Rh, IgG andtibodies cross the placenta and attach to fetal erythrocytes
    • Antibody production occurs in Rh-mothers and have Rh+ babies, not the other way around
    • Rh incompatibility can lead to:
    •   -severe anemia, edema, CNS damage, and fetal death
    •   -other names: erythroblastic fetalis and hydrops fetalis
  57. True or False
    For HDN to occur the mom has to be Rh- and the dad has to be RH+.
  58. Sickle Cell Anemia
    • -Autosomal recessive
    • -Defective hemoglobin- hemoglobin S, Hgb S
    • Hgb S forms when valin replaces glutamic acid in the hemoglobin molecule
    • -During episodes of deoxygenation and dehydration, thie erythrocyte  can stretch and solidify into and elongated sickle shape
    • This cell is susceptible to splenic sequestration and can cause Vasoocclusive crisis (sickle cell crisis) blocks vessels
  59. Thalassemia
    • -Autosomal recessive
    • -Minor and Major
  60. Thalassemia Minor
    • -Heterozygous
    • -Usually asymptomatic
    •   -maybe and enlarged spleen and slightly smaller RBCs
  61. Thalassemia Major
    • -Homozygous
    • -Severe anemia
    • -Regular transfusions required
  62. Hemophilia A
    • Classical hemophilia
    • -X-linked recessive deficiency of factor VIII (8)
    • -1:5000-10,000 male births
  63. Hemophilia B
    • X-linked recessive deficiency of factor IX (9)
    • 1-30,000 male births
  64. Red Blood Cells (RBC)
    • -Erythrocytes
    • -lifespan 80-120 days
    • -function in gas transport
    • 1-high surface-to-volume ratio
    • 2- demonstrate reversible deformityCount: 4.00-6.00 x 10^6/mm^3 (4-6 million/millimeter cubed)
  65. Hydrops fetalis
    Fetuses that do not survive anemia in utero usually are stillborn with gross edema in the entire body
  66. Erythroblastosis Fetalis
    Another term for hemolytic disease of the newborn
  67. Poikilocytosis
    Assuming various shapes
  68. Anisopoikilocytolysis
    Varying sizes and abnormal shapes
  69. Anisocytolysis
    Assuming various sizes
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Patho unit 3 ch20&21
2013-10-01 21:58:01
Patho unit partch20 21

Patho unit 3 ch20&21
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