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Development of a RBC
- Pleuripotent stem cell stimulated by EPO => committed erythroid precursor
- Maturation of Erythroblast
- Nucleus extruded
- Reticulocytes released into blood stream ~ 7 days
- Reticulocytes converted to RBC ~ 24-48 hours
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Diseases that occur due to dysfunction of RBC production
- Anemia
- Mutations of hemoglobin
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Anemia
- abnormally low level of circulating RBCs or RBCs with diminished level of hemoglobin
- Women < 12g/dL
- Men < 13 g/dL
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Causes of Anemia
- Excessive blood loss
- over destruction of RBC in periphery or spleen
- Deficient RBC production
-
Manifestations of Anemia
- Decreased presence of hemoglobin in the blood - Pallor
- Tissue hypoxia due to deficient oxygen transport
- Recruitment of compensatory mechanisms
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Effects of tissue hypoxia
- weakness
- fatigue
- angina
- - small microvasculature in heart very sensitive to changes in O2
- - sends signal to brain that there is "pain"
- headache
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Compensatory mechanisms for Anemia
- tachycardia
- palpitations
- dyspnea
- bone pain (also a side effect of EPO)
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Blood loss anemia
- Rapid blood loss = hypovolemic shock
- Slow blood loss = may have no symptoms
- - GI Bleed
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Hemolytic Anemia
- Premature destruction of RBCs
- Increased iron in blood due to destruction of RBCs
- Intrinsic = hereditary = fatal
- Extrinsic = medications, infection, blood clots
- -RBC reaches site and is destroyed
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Sickle Cell Disease
- Inherited disorder resulting in abnormal hemoglobin and hemolysis; 2 genes
- Point mutation in beta-chain of the hemoglobin molecule
- Protective against malaria
- Poor O2 carrying capacity
-
Clinical course of sickle cell
- Hemolytic anemia
- Chronic hyperbilirubinemia
- Vaso-occlusive disease/crisis
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Presenting symptoms of hemolitic anemia associated with sickle cell disease
fatigue, pallor, angina, palpitations
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Presenting symptoms of chronic hyperbilirubinemia associated with sickle cell disease
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Presenting symptoms of vaso-occlusive disease/crisis associate with sickle cell disease
- Pain
- Kidney disease
- infarct
- eye disease
- splenic enlargement/injury
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B-Thalassemia
- Defect in B-chain synthesis
- More comon in mediterranean countries
- Damaged RBC membranes
- Increased destruction in the spleen
- Coagulation abnormalities => increased risk for thrombosis
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Clinical Manifestation of B-Thalessemia minor
- sufficient normal Hgb synthesis
- only a problem in crisis
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Clinical Manifestations of B-Thalassemia Major
- Severe transfusion dependant anemia
- mpaired bone growth
- splenic enlargement
- blood transfusion is the only treatment
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Alpha - Thalassemia
- Defect in the alpha chain synthesis
- 1 gene deletion; asymptomatic
- 2 gene deletion; mild hemolytic anemia
- 3 gene deletion; alpha chain aggregates, moderate hemolytic anemia
- 4 gene deletion; death
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G6PD Deficiency
- NADP not converted to NADPH in RBC
- NADPH protects cells from oxidative damage
- Oxidation converts hemoglobin to methemoglobin which inhibits O2 carrying capacity
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Causes of Iron Deficiency Anemia
- Dietery deficiency
- Poor absorption (acholoric state)
- Pregnancy
- Gastrointestinal loss (bleed)
- Menstruation
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Clinical manifestations of Iron-Deficiency Anemia
- Low hemoglobin / hematocrit
- Decreased iron stores
- low serum iron and ferritin(carries iron)
- fatigue, pallor, palpitations
- deformity of fingernails
- pica
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Megaloblastic Anemias
- Enlarged immature RBCs
- Slow-developing
- Usually related to age or medication use
- B12 deficiency
- Folic Acid deficiency
-
Manifestations of B12 deficiency megaloblastic anemia
- Often asymptomatic
- Neurologic disease
- Glossitis
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Manifestations of Folate Deficiency Megaloblasic Anemia
Irritability
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Aplastic Anemia
- Complete bone marrow stem cell reduction or suppression
- High-dose radiation
- Chemotherapy
- Chloramphenicol
- Complications of severe illness
-
Manifestations of Aplastic Anemia
- Weakness, fatigue, pallor
- petechiae
- unexplained bleeding or ecchymoses
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Anemia of Chronic Disease
- common in patients with kidney disease
- inadequate production of epo or body not responding to epo
- chronic infection
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Five Stages of Hemostasis
- Vessel spasm
- formation of the platelet plug
- blood coagulation
- blot retraction
- clot dissolution
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Hypercoagulability
- exaggerated form of hemostasis
- increased platelt function or accelerated activity of the clotting system
- Risk for DVT and PE
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Thrombocytosis
- Increased platelets
- Chronic or Reactive
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Reactive Secondary Thromocytosis
- increased platelets in response to stimuli
- tumor, infection, trauma...
- overproduction of inflammatory cytokines
- common in hospitalized patients
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Inherited increased clotting activity
- mutations in factor 5 or prothrombin gene
- antiphospholipid syndrome
- increased risk for thromboembolic event
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Acquired increased clotting activity risk factors
- venous stasis
- MI
- Oral contraceptives
- Smoking
- Obesity
- Cancer &pregnancy
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Bleeding disorders
- impairment of blood coagulation
- thrombocytopenia
- decreased coagulation factors
- decreased vessel integrity
- spontaneous bleeding
- aquired disorders more common
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Immune Thrombocytopenic Purpura
- Acute and chronic
- autoantibodies to platelets
- complex trapped in spleen and removed
- antibodies directed at platelets
- treatment aimed at reducing immune activity
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Drug - Induced Thrombocytopenia
- Drug-induced antibodies to platelets
- Complex trapped in spleen and removed
- uniqe reaction with heparin inducing hypercoaguable state
- treatment aimed at removing offending agent
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Thromotic Thrombocytopenia Purpura
- Rare, Aquired disorder
- increased recruitment of platelet aggregating substances
- hemolytic anemia, renal failure, fever and neurologic problems
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Von willebrand disease
- most frequent inherited bleeding disorder
- DDAVP is the drug of choice
- inability to stabilize hemostatic plug or anchor clot
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Hemophilia
- lack of factor 8 hemophilia a
- lack of factor 9 hemophelia b
- typically expressed in males
- effects early clotting cascade
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Bleeding of hemophilia
- joint bleeding
- muscle bleeding
- chronic pain
- muscle atrophy
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