genetic disorders of hemoglobin ppt

... Chapter 099. Disorders of Hemoglobin (Part 1) Harrison's Internal Medicine > Chapter 99. Disorders of Hemoglobin Disorders of Hemoglobin: Introduction Hemoglobin is critical ... stigmata. Hemoglobin Structure Different hemoglobins are produced during embryonic, fetal, and adult life (Fig. 99-1). Each consists of a tetramer of globin polypeptide chains: a pair of α- like ... alter clinical behavior. Function of Hemoglobin To support oxygen transport, hemoglobin must bind O 2 efficiently at the partial pressure of oxygen (P O2 ) of the alveolus, retain it, and release...

Ngày tải lên: 07/07/2014, 04:20

... biosynthesis) and of structural hemoglobinopathies (e.g., an abnormal amino acid sequence). Hereditary persistence of fetal hemoglobin (HPFH) is characterized by synthesis of high levels of fetal hemoglobin ... Hereditary persistence of fetal hemoglobin persistence of high levels of HbF into adult life V. Acquired hemoglobinopathies A. Methemoglobin due to toxic exposures B. Sulfhemoglobin due to ... life. Acquired hemoglobinopathies include modifications of the hemoglobin molecule by toxins (e.g., acquired methemoglobinemia) and abnormal hemoglobin synthesis (e.g., high levels of HbF production...

Ngày tải lên: 07/07/2014, 04:20

... of the complete blood cell count (e.g., profound microcytosis with minimal anemia in thalassemia trait). Detection and Characterization of Hemoglobinopathies—General Methods Of the ... mutant hemoglobins can usually be characterized by more specialized techniques such as isoelectric focusing and/or high-pressure liquid chromatography (HPLC). Quantitation of the hemoglobin profile ... The number of severe cases of thalassemia in the United States is about 1000. Sickle cell disease is the most common structural hemoglobinopathy occurring in heterozygous form in ~8% of American...

Ngày tải lên: 07/07/2014, 04:20

... important for prognosticating the clinical severity of disease. Chapter 099. Disorders of Hemoglobin (Part 6) Clinical Manifestations of Sickle Cell Anemia Most patients with sickling ... increase in the hematocrit and feedback inhibition of reticulocytosis might be beneficial, even at the expense of increased blood viscosity. The role of adhesive reticulocytes in vasoocclusion might ... invariably produces wide analysis will yield individualized profiles that predict a patient's clinical course. Nevertheless, a number of interesting patterns have emerged from these modifying...

Ngày tải lên: 07/07/2014, 04:20

... tests already discussed. Thorough characterization of the exact hemoglobin profile of the patient is important, because sickle thalassemia and hemoglobin SC disease have distinct prognoses or ... of retinopathy; antibiotic prophylaxis appropriate for splenectomized patients during dental or other invasive procedures; and vigorous oral hydration during or in anticipation of periods of ... syndromes are suspected on the basis of hemolytic anemia, RBC morphology (Fig. 99-4), and intermittent episodes of ischemic pain. Diagnosis is confirmed by hemoglobin electrophoresis and the...

Ngày tải lên: 07/07/2014, 04:20

Ngày tải lên: 10/08/2014, 15:20

Ngày tải lên: 10/08/2014, 15:20

Ngày tải lên: 10/08/2014, 15:20

Ngày tải lên: 10/08/2014, 15:20

... the ability of hemoglobin to deliver more oxygen to tissues at low pH. It arises from the stabilizing action of protons on deoxyhemoglobin, which binds protons more readily than oxyhemoglobin ... the tetrameric structure of the proteins, the proper arrangement of the charged amino acids, and interaction with protons or 2,3-BPG. Developmental Biology of Human Hemoglobins Red cells first ... globin genes partially after birth. Genetics and Biosynthesis of Human Hemoglobin Normal red blood cell (RBC) differentiation requires the coordinated expression of the globin genes with the genes...

Ngày tải lên: 07/07/2014, 04:20

... C:50% Pathophysiology of sickle cell crisis. Several sickle syndromes occur as the result of inheritance of HbS from one parent and another hemoglobinopathy, such as β thalassemia ... Chapter 099. Disorders of Hemoglobin (Part 5) Sickle Cell Syndromes The sickle cell syndromes are caused by a ... reticulocytes) that are abnormally adherent to the endothelium of small venules. These abnormalities provoke unpredictable episodes of microvascular vasoocclusion and premature RBC destruction...

Ngày tải lên: 07/07/2014, 04:20

... therapy of sickle cell anemia has been the introduction of hydroxyurea as a mainstay of therapy for patients with severe symptoms. Hydroxyurea (10–30 mg/kg per day) increases fetal hemoglobin ... received kidney transplants, but they often experience an increase in the frequency and severity of crises, possibly due to increased infection as a consequence of immunosuppression. The most significant ... pathogenesis of sickle cell crisis, and their suppression may be an important benefit of hydroxyurea therapy. Hydroxyurea should be considered in patients experiencing repeated episodes of acute...

Ngày tải lên: 07/07/2014, 04:20

... aid in control. Chapter 099. Disorders of Hemoglobin (Part 9) Unstable hemoglobins occur sporadically, often by spontaneous new mutations. Heterozygotes are often symptomatic because a significant ... complications of chronic hemolysis, even if anemia is absent. Precipitation of unstable hemoglobins is aggravated by oxidative stress, e.g., infection, antimalarial drugs. High-O 2 affinity hemoglobin ... variant accounts for a portion of the total hemoglobin. Symptomatic unstable hemoglobins tend to be β-globin variants, because sporadic mutations affecting only one of the four α-globins would...

Ngày tải lên: 07/07/2014, 04:20

... inherited disorders of α- or β-globin biosynthesis. The reduced supply of globin diminishes production of hemoglobin tetramers, causing hypochromia and microcytosis. Unbalanced accumulation of α ... critical clue. The best diagnostic test is methemoglobin assay, which is usually available on an emergency basis. Methemoglobinemia often causes symptoms of cerebral ischemia at levels >15%; ... which the synthesis of the affected globin is impaired, altered synthesis of other globin chains, and co- inheritance of other abnormal globin alleles. Clinical Manifestations of β-Thalassemia...

Ngày tải lên: 07/07/2014, 04:20

... b 90–95% of the hemoglobin is hemoglobin Barts (tetramers of γ-chains). α-Thalassemia-2 trait is an asymptomatic, silent carrier state. α- Thalassemia-1 trait resembles β-thalassemia minor. Offspring ... hemolytic anemia but Chapter 099. Disorders of Hemoglobin (Part 11) Severity is highly variable. Known modulating factors are those that ameliorate the burden of unpaired α-globin inclusions. ... associated with milder synthetic defects and co-inheritance of α-thalassemia trait reduce clinical severity by reducing accumulation of excess α globin. HbF persists to various degrees in β-thalassemias....

Ngày tải lên: 07/07/2014, 04:20

... that affect the LCR of the α-globin gene cluster. Diagnosis and Management of Thalassemias The diagnosis of β-thalassemia major is readily made during childhood on the basis of severe anemia ... the characteristic signs of massive ineffective erythropoiesis: hepatosplenomegaly, profound microcytosis, a characteristic blood smear (Fig. 99-5), and elevated levels of HbF, HbA 2 , or both. ... maintain a hematocrit of at least 27–30% so that erythropoiesis is suppressed. Splenectomy is required if the annual transfusion requirement (volume of RBCs per kilogram of body weight per year)...

Ngày tải lên: 07/07/2014, 04:20

... hypochromia, and hemoglobin levels rarely <1 g/L (<10 g/dL). Hereditary Persistence of Fetal Hemoglobin HPFH is characterized by continued synthesis of high levels of HbF in adult life. ... metering pump. The constant presence of the drug improves the efficiency of chelation and protects tissues from occasional releases of the most toxic fraction of iron—low-molecular-weight iron—which ... available. Cardiac toxicity is often insidious. Early development of pericarditis is followed by dysrhythmia and pump failure. The onset of heart failure is ominous, often presaging death within...

Ngày tải lên: 07/07/2014, 04:20

... al: Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Blood 99:10, 2002 [PMID: 11756146] Chapter 099. Disorders of Hemoglobin (Part ... 485–510 Steinberg MH, Benz EJ Jr: Pathobiology of the human erythrocyte and its hemoglobins, in Hematology: Basic Principles and Practice , 3d ed, R Hoffman et al (eds). New York, Churchill Livingstone, ... 2003 [PMID: 14693325] DeSimone J et al: Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia. Blood 99:3905, 2002 [PMID: 12010787]...

Ngày tải lên: 07/07/2014, 04:20

... text. GRAPHICS The Gale Encyclopedia of Genetic Disorders con- tains over 200 full color illustrations, including photos GALE ENCYCLOPEDIA OF GENETIC DISORDERS ix INTRODUCTION toms of acromegaly can be halted ... ENCYCLOPEDIA OF GENETIC DISORDERS xiii ADVISORY BOARD An advisory board comprised of genetic specialists from a variety of backgrounds provided invaluable assistance in the for- mulation of this encyclopedia. ... CT GALE ENCYCLOPEDIA OF GENETIC DISORDERS xv CONTRIBUTORS Craniofacial ã Malformed ears. Abnormalities of the ears, when pres- ent, involve both ears but may show different levels of severity ranging...

Ngày tải lên: 10/08/2014, 15:20

Ngày tải lên: 10/08/2014, 15:20