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Unit 4A - Alterations in Alterations in Hematologic...

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Unformatted text preview: Alterations in Alterations in Hematologic Function Objectives Objectives Differentiate between various types of anemias. Define myeloproliferative disorders. Differentiate between various disturbances in leukocyte function. Describe various conditions associated with platelet dysfunction RBC Lab Values RBC Lab Values Red blood cell (RBC) count – – – Men:4.6–6.2 million RBCs per microliter (µL) Women: 4.2–5.4 million RBCs per µL Children:4.6–4.8 million RBCs per µL Hemoglobin – Men:14–18 grams per deciliter (g/dL) – Women:12–16 g/dL Hematocrit – – – – Men:40%–54% Women:37%–47% Children:31%–41% Newborns:44%–64% Anemia Anemia Decrease in circulating erythrocytes Decrease in the quality or quantity of Hgb. Classified according to the effect on cell size (cytic) or Hgb concentration (chromic) – Example macrocytic­normochromic anemia Large (abnormally shaped erythrocytes) with normal hemoglobin concentration. Clinical Manifestations Clinical Manifestations Tissue hypoxia: ↓ 02 carrying capacity in the blood Symptoms depend on the body’s ability to compensate and may increase as RBC production continues to decrease. Decreased RBC → decreased consistency and volume of blood. – Early compensation → movement of interstitial fluid into the blood to increase plasma volume and maintain an adequate volume, – Blood viscosity ↓ leads to hyperdynamic state that causes ↑ HR and ↑ stroke volume. Can become pathologic if not corrected (cardiac dilation and heart valve insufficiency) Clinical Manifestations (cont.) Clinical Manifestations (cont.) Hypoxemia: contributes to C­V dysfunction by ↑ blood flow through arterioles, capillaries and venules →↑venous return, contributes to ↑ HR and stroke volume Rate and Depth of Breathing ↑: (tachypnea) Dizziness Fatigue Sometimes symptoms are only present with ↑ exertion. Pale mucous membranes, lips, conjunctiva or yellow (jaundice) due to RBC destruction (hemolysis) Nervous system changes (parasthesias) Abdominal pain, nausea, vomiting Fever Severe: Decreased blood flow in the kidneys→renin­angiotensin response (Na+ and H20 retention) Macrocytic­Normochromic Anemias Macrocytic­Normochromic Anemias Large erythrocytes with normal Hgb content. Result of ineffective erythrocyte DNA synthesis→ die prematurely, decrease in circulating number. RBC growth and development proceed at unequal rates. – Due to B12 deficiency (Pernicious anemia) – Due to Folate deficiency Pernicious Anemia Pernicious Anemia Etiology: absence of Intrinsic Factor (enzyme for absorption of B12 in stomach.) Congenital Chronic Gastritis Gastrectomy Diagnostic Work­up Blood test Bone Marrow aspiration Gastric biopsy Clinical presentation Schilling Test Signs/Symptoms: Develops slowly Early S/S non­specific Classic S/S of anemia Beefy, red, smooth tongue Sallow appearance Hepatomegaly Treatment Life long B12 injections Folate Deficiency Anemia Folate Deficiency Anemia Etiology: Inadequate folate intake in the diet Diagnostic work­up: – Serum folate level – Clinical presentation Signs/Symptoms: Similar to pernicious anemia, but no neurologic symptoms Stomatitis Ulcerations of the mouth Treatment – Folate administration PO (by mouth) until levels return to normal. Microcytic­Hypochromic Anemias Microcytic­Hypochromic Anemias Small erythrocytes with lower than normal Hgb. Result from: Disorders of iron metabolism Disorders of porphyrin and heme synthesis Disorders of globin synthesis. Examples – Iron Deficiency Anemia – Thalassemia: genetic disorder Iron Deficiency Anemia Iron Deficiency Anemia Most common type of anemia Females > Males Causes: Pregnancy Loss of blood GI bleeding Low iron intake Pica Signs/Symptoms Diagnostic Work­up Direct: Bone Marrow Bx Indirect: serum transferrin, transferrin saturation, total iron binding capacity (TIBC), free erythrocyte protoporphyrin(FEP) Identify/treat underlying cause – – – – Initially non­specific Fatigue, weakness SOB Later: changes to fingernails (koilonychia), burning and soreness of the tongue (glossitis) Treatment – Iron Replacement Therapy PO or IV Normocytic­Normochromic Normocytic­Normochromic Anemias Erythrocytes are normal in size and Hgb is normal in content, but insufficient in number. Do not share etiology, pathologic or morphologic manifestations as other anemias. Include: – – – – Aplastic anemia Post­hemorrhagic anemia Hemolytic anemia Anemia of chronic inflammation (disease) Myeloproliferative RBC Myeloproliferative RBC disorders Excessive RBC production: polycythemias Polycythemia: – Primary: Polycythemia Vera – Secondary: Due to hypoxia from high altitudes, COPD, or coronary heart failure, causing ↑erythropoietin secretion. – Relative polycythemia: hemoconcentration associated with dehydration Polycythemia Vera Polycythemia Vera Chronic overproduction of RBC Splenomegaly Rare: males of eastern European descent Nonmalignant abnormal proliferation of bone marrow stem cells with subsequent self­destructive expansion of RBCs. Erythropoietin levels remain normal. Genetic cause: most likely Clinical manifestations­ Clinical manifestations­ Polycythemia Vera Increase blood volume→ ↑ blood viscosity →hypercoagulable state → clogged or occluded blood vessels → tissue ischemia and infarction Ruddy complexion of face, hands, feet , ears HA, drowsiness, visual disturbances, delirium Elevated BP, angina, Raynaud’s phenomenon. Itching (due to mast cell concentration in the skin) intensified by water or heat. Diagnostic Work­up Diagnostic Work­up ↑ RBCs ↑ Total blood volume Possible ↑ platelets and WBCs Treatment Treatment Therapeutic phlebotomy: removal of 300 – 500 ml of blood. Radioactive phosphorus: suppress erythropoiesis—can result in acute leukemia. Myelosuppressing agent: Hydroxyurea Immunosuppressive therapy: Interferon: decreases clinical and lab manifestations of myeloproliferation. Sickle Cell Anemia Sickle Cell Anemia Sickle cell anemia A group of disorders characterized by the production of abnormal hemoglobin S HgS is formed by a genetic mutation that causes valine to replace glutamic acid in genetic structure Altered molecular structure of RBC causing abnormal cell shape with susceptibility to damage, lysis and phagocytosis RBC sickling causes vascular occlusion, ischemia and pain Prone to MI and stroke (CVA) Normal cells are round, sickle cells Normal cells are round, sickle cells are abnormally shaped and rigid Leukocyte Alterations Leukocyte Alterations Leukocytosis: above normal WBCs Leukopenia: below normal WBCs Granulocytosis: above normal granulocytes (neutrophils, basophils, eosinophils) Neutrophilia: elevated neutrophils (seen in early inflammation/infection) Neutropenia: below normal neutrophils Eosinophilia: elevated eosinophils (allergic reactions­ asthma, hay fever or parasitic infection. Pancytopenia: a reduction in all cellular components of the blood. Left Shift or Leukemoid Left Shift or Leukemoid Reaction Increase in immature neutrophils/leukocytes when the demand for circulating mature neutrophils/leukocytes exceeds the supply. Leukemias Leukemias Clonal malignant disorder of the blood and blood – forming organs. Uncontrolled proliferation of malignant leukocytes→ overcrowds the bone marrow leads to ↓ production and function of normal hematopoietic cells. Acute leukemias: rapid growth of immature cells – Acute lymphocytic leukemia (ALL) – Acute myelogenous leukemia (AML) Chronic leukemias: slow growth of more differentiated cells. – Chronic lymphocytic leukemia (CLL) – Chronic myelogenous leukemia (CML) Leukemias Leukemias Incidence: slightly higher males over females ALL: Most common children(78% of all cases diagnosed). CLL and AML: most common in adults Familial tendency Increased tendency with other hereditary abnormalities Genetic translocation: errors in mitosis Risk factors for Leukemias Risk factors for Leukemias Environmental – Cigarette smoke – Exposure to benzene – Ionizing radiation Disease­related – – – – HIV Hepatitis C Human T­cell leukemia­lymphoma virus(HTLV­1) Acute leukemia can develop secondary to certain acquired disorders (i.e.CML, CLL, polycythemia vera) Medication related – – Medications that cause bone marrow suppression Treatment of one cancer can lead to secondary cancer Acute Leukemias Acute Leukemias Characterized by undifferentiated and immature cells—blast cells Abrupt and rapid onset Short survival times 85% ALL→ B cells 15% from T cells Children < 15: 1/3 of all cancer deaths Incidence increases after age 50. Clinical Presentation Clinical Presentation Bone marrow depression (i.e. fatigue, bleeding, petechiae, ecchymosis, hematuria) Infection: Fever with chills Anorexia Liver, spleen, lymph node enlargement Neurological impairment: HA, vomiting, papilledema, visual and auditory disturbances Treatment Treatment Chemotherapy Supportive treatment: transfusions, antibiotics, antifungals, antivirals Bone marrow transplant Hematopoietic medications: used to stimulate blood cell growth Chronic Leukemia Chronic Leukemia CML and CLL Cells are well­differentiated Longer life expectancy (usually years) Majority of leukemia seen in adults. Develops slowly and insidiously. Clinical Presentation Clinical Presentation Splenomegaly Fatigue Weight loss Night sweats Low grade fever Philadelphia Chromosone: CML CLL: malignant transformation of B cells: suppresses normal antibody production. Treatment Treatment Bone marrow transplant Biologic response modifiers: arouse body’s response to infection Chemotherapeutic agents: combination therapy Radiation Therapy Malignant Lymphomas Malignant Lymphomas Lymphadenopathy: enlarged lymph nodes – Localized or generalized – Due to inflammation, malignancy, endocrine disorders or lipid storage diseases. Develop from proliferation of malignant lymphocytes in the lymphatic system – Hodgkin lymphoma – B cell neoplasms (AKA Non­Hodgkin’s lymphoma) which include T cell and NK­cell neoplasms, and multiple myelomas Lymphadenopathy Lymphadenopathy Source: med.cmu.ac.th Pathogenesis of Hodgkin’s Pathogenesis of Hodgkin’s Disease Presence of Reed­Sternberg cells – Malignant transformation of normal cells – Transformed cells secrete cytokines Cause inflammation locally and systemically Neoplastic development unclear – Arises from B cell Clinical Manifestations Hodgkin Clinical Manifestations Hodgkin Lymphoma Enlarged painless mass in the neck (often 1 st sign) Mediastinal mass (may cause cough, chest pain, shortness of breath) Enlarged cervical, axillary, inguinal, retroperitoneal lymph nodes “B” symptoms (advanced disease) – – – – Fever Drenching night sweats Weight loss > 10% past 6 months Itchy skin Cotswold Staging of Hodgkin’s Cotswold Staging of Hodgkin’s Disease Stage I – Single lymph node region Stage II – > 2 lymph node regions on SAME side of diaphragm Stage III – Lymph nodes on BOTH sides of diaphragm Stage IV – Extranodal sites distant from known nodal site – Systemic symptoms Source: encognitive.com Cotswald’s Staging Cotswald’s Staging Modifying characteristics applied to any stage: – A: no systemic symptoms – B: fever > 380 C., drenching night sweats, weight loss > 10% in past 6 months – E: extranodal contiguous extension that can be encompassed within a radiation field appropriate for nodal disease of the same extent – X: presence of “bulky” disease, i.e., mediastinal mass with maximum width >/= 1/3 of the internal transverse diameter of the thorax at T5­6 Treatment Treatment 75% cure rate Radiation Chemotherapy B­cell Neoplasms B­cell Neoplasms (Non­Hodgkin lymphoma) Usually found in age > 50 May be due to: – Family history – Irradiation – Infection with cancer­related viruses (HIV, HTLV­1, hepatitis C) – H. Pylori bacteria (gastric lymphomas) Clinical Manifestations Clinical Manifestations B­cell Neoplasms Enlarged painless lymph nodes – If abdominal nodes affected, Distended abdomen Fluid accumulation – Chest pain if thymus involved Fever Drenching night sweats Fatigue Loss of appetite Red patches on skin Intense pruritis Treatment Treatment Chemotherapy Radiation therapy Autologous stem cell transplants Monoclonal antibodies (i.e.Rituxan) Survival – Nodular disease > diffuse disease Multiple Myeloma Multiple Myeloma B­cell cancer Malignant plasma cells infiltrate bone marrow and aggregate into tumor masses throughout skelatal system. Produce large amounts of immunoglobulin (IgG). Cytokines (IL6) aid in growth and survival of MM cells­M­ protein: most prominent protein in the blood in MM. Neoplastic cells: found in bone marrow not in blood. Myeloma cells: stimulate osteoclasts to reabsorb bone →bone lesions and hypercalcemia (due to cytokines in →bone myeloma cells) myeloma Chromosonal translocation­genetic alteration Bence­Jones protein in the urine and blood Multiple Myeloma Multiple Myeloma Clinical Presentation Hypercalcemia Pathologic fractures Bone lesions Bone pain Renal failure Proteinuria Hyperviscosity syndrome Bence­Jones protein in the urine/serum Treatment Prognosis poor – Treatment includes: Chemotherapy Bone marrow transplant Palliative RT Coagulation Defects Coagulation Defects Normal Platelet Function Normal Platelet Function Platelets are bits of megakaryocyte membrane containing cytoplasm but no organelles Platelets circulate for 7­14 days before losing functional ability Platelet production is stimulated by thrombopoietin produced by liver Platelets bind thrombopoietin; when platelet count falls, thrombopoietin is available to stimulate bone marrow production Figure 14-4 Coagulation cascade. PTT, Partial thromboplastin time; PT, prothrombin time. Elevated PT (Normal Platelets, Elevated PT (Normal Platelets, and PTT) Extrinsic pathway abnormality Factor VII deficiency Liver disease Vitamin K deficiency Coumadin effect Elevated PTT (Normal Elevated PTT (Normal Platelets, PT) Intrinsic pathway abnormality Hemophilia (VIII, IX) von Willebrand disease Lupus anticoagulant Heparin effect Increased Bleeding Time Increased Bleeding Time (Normal Platelets, PT, PTT) Platelet defect Platelet­inhibiting drugs (ASA, NSAIDs) von Willebrand disease Thrombocytopenia Thrombocytopenia Platelet count < 150,000/mm3 Symptoms when platelet count < 100,000/mm3 Hemorrhage risk at 50,000/mm3 with minor trauma Spontaneous bleeding at 10,000/mm3 Clinical manifestations: frank bleeding, ecchymosis, purpura, petechiae) Petechiae Purpura Ecchymosis Thrombocytopenia Thrombocytopenia Pathophysiology Congenital (rare) or Acquired (viral infections, drug reactions, autoimmune diseases, nutritional deficits, cancer, anemia, chronic renal failure). Usually results from: – Decrease platelet production – Increased platelet consumption – Combination of both Thrombocytopenia (cont.) Thrombocytopenia (cont.) Decreased platelet production: – Nutritional deficiencies (B12, folate) – Infection (HIV) – Meds (thiazides) – Chemotherapeutic agents – RT – Chronic renal failure – Bone marrow infiltration by cancers – Aplastic anemia Increased platelet consumption – Heparin induced thrombocytopenia (HIT) – Idiopathic thrombocytopenia purpura (ITP) – Thrombotic thrombocytopenia purpura (TTP) – Disseminated intravascular coagulation (DIC) HIT HIT Cause: Heparin administration Immune mediated adverse drug reaction Caused by IgG antibodies against heparin platelet factor 4 complex. Platelet aggregation→ add’l platelet factor 4 + thrombin activation → thrombocytopenia 5­10 days after administration. Hallmark of HIT: thrombocytopenia If untreated → Intravascular aggregation of platelets → arterial/venous* thrombosis Can present with: DVT, PE, limb ischemia, CVA, MI Labs: Measure serum heparin­platelet 4 factor antibodies (ELISA) Treatment: D/C heparin, alternative anticoagulation ITP ITP Acute: in children or 2º to infections, meds, SLE Chronic: autoantibodies (IgG class) against platelet antigens. Ab bind directly to the platelet Ag → antibody coated platelets are recognized and removed by macrophages in the spleen. Signs/Symptoms: minor bleeding to major hemorrhage from mucosal sites Diagnosis: bleeding hx, CBC, evidence of past infections Treatment: palliative→ focuses on prevention of platelet destruction Steroids: suppress the immune response IV Immunoglobulins Splenectomy: considered DIC DIC Thrombohemorrhagic Disorder Activation of coagulation resulting in fibrin formation and clotting in medium /small vessels in the body. Can result in multi­system organ failure Widespread clotting→ consumption of platelets and clotting factors → severe bleeding. DIC DIC landesbioscience.com What causes DIC? What causes DIC? Malignancy Infections Pregnancy complications Severe trauma Liver disorders Intravascular hemolysis Hypoxia and low blood flow Clinical Manifestations Clinical Manifestations Widespread hemorrhage Oozing from puncture sites, incisions, mucous membranes CNS: altered states of consciousness GI: bleeding, distention Pulmonary: infarctions, ARDS, hypoxemia Renal: hematuria, oliguria, renal failure Integumentary: vascular lesions, gangrene, ecchymotic lesions (purpura, petechiae), hematomas Bleeding from 3 or more unrelated sites. Thromboembolic Disorders Thromboembolic Disorders Thrombus: clot attached to a vessel wall Venous Thrombus: RBCs with larger amounts of fibrin, less platelets Arterial Thrombus: platelet aggregates held together with thrombin Thrombus reduces or obstructs blood flow to tissues and organs. Embolus: thrombus detaches from the wall of the vessel and becomes lodged in the smaller blood vessels. Can be life threatening depending on where the embolus lodges. Virchow Triad Virchow Triad Risk for thrombus formation Injury to the blood vessel – Due to atherosclerosis, HTN, injury to the b.v. endothelium Abnormalities of blood flow – Turbulence in arterial flow or stasis in venous flow Hypercoagulability of blood – Risk for thrombosis­ can be hereditary hypercoagulability (protein C, protein S deficiency) OR acquired( antiphospholipid syndrome) Common causes: surgery, MI,CHF, limb paralysis, spinal cord injury, malignancy, age, prolonged immobility. ...
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