DISORDERS OF HEMOGLOBIN GENETICS PATHOPHYSIOLOGY

Chapter 062. Principles of Human Genetics (Part 24) Nucleotide Repeat Expansion Disorders Several diseases are associated with an increase in the number of nucleotide repeats above a certain threshold (Table 62-6). The repeats are sometimes located within the coding regi[r]

behaves like moderately unstable hemoglobin. Patients with HbH disease should undergo splenectomy if excessive anemia or a transfusion requirement develops. Oxidative drugs should be avoided. Iron overload leading to death can occur in more severely affected patients. Prevention Antenatal dia[r]

102Asn -> Lys)] bind sufficient oxygen in the lungs, despite their lower oxygen affinity, to achieve nearly full saturation. At capillary oxygen tensions, they lose sufficient amounts of oxygen to maintain homeostasis at a low hematocrit (Fig. 99-2) (pseudoanemia). Capillary hemoglo[r]

Chapter 099. Disorders of Hemoglobin (Part 10) Low-affinity hemoglobins should be considered in patients with cyanosis or a low hematocrit with no other reason apparent after thorough evaluation. The P50 test confirms the diagnosis. Counseling and reassurance are the interventi[r]

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. Alleles associated with milder synthetic defects and co-inheritance of α-thalassemia trait re[r]

interaction of HbE with β-thalassemia rather than HbE homozygosity, a condition associated with asymptomatic microcytosis, hypochromia, and hemoglobin levels rarely <1 g/L (<10 g/dL). Hereditary Persistence of Fetal Hemoglobin HPFH is characterized by contin[r]

)], or disrupt interactions of the hydrophobic pockets of the globin subunits with heme [e.g., Hb Koln (β98Val -> Met)] (Table 99-3). The inclusions, called Heinz bodies, are clinically detectable by staining with supravital dyes such as crystal violet. Removal of these i[r]

Chapter 099. Disorders of Hemoglobin (Part 14) Deferasirox is a promising oral iron-chelating agent. Single daily doses of 20 or 30 mg deferasirox produced reductions in liver iron concentration comparable to desferoxamine in chronically transfused adult and pediatric pa[r]

disease prevention. Genetics has traditionally been viewed through the window of relatively rare single-gene diseases. Taken together, these disorders account for ~10% of pediatric admissions and childhood mortality. It is, however, increasingly apparent that virtually ev[r]

abnormalities, both expressive and receptive language deficits should be monitored. Typically, infants start to babble by 6 months of age, followed by advances in complexity which includes several phonemes. Later, jargoning (i.e. adds inflection to utterances in an attempt to tell a story) de[r]

activity of the sympathoadrenal system (SAS) triggers complex pathways. The long-lasting activation of these mechanisms may lead to their fixation, enabling the pressure to serve as a tool for increasing the natriuresis at general load. Biological systems, which are considered to be ou[r]

The agrammatical variant is also known as progressive nonfluent aphasia and displays similarities to Broca's aphasia. However, dysarthria is usually absent. The semantic variant of PPA is also known as semantic dementia and displays similarities to Wernicke's aphasia, but the comprehension di[r]

HbS, hemoglobin sickling B. Altered O2 affinity 1. High affinity—polycythemia 2. Low affinity—cyanosis, pseudoanemia C. Hemoglobins that oxidize readily 1. Unstable hemoglobins—hemolytic anemia, jaundice 2. M hemoglobins—methemoglobinemia, cyanosis II. Thalassemias—defective biosynthe[r]

Chapter 099. Disorders of Hemoglobin (Part 1) Harrison's Internal Medicine > Chapter 99. Disorders of Hemoglobin Disorders of Hemoglobin: Introduction Hemoglobin is critical for normal oxygen delivery to tissues; it is als[r]

Chapter 099. Disorders of Hemoglobin (Part 2) Figure 99-2 Hemoglobin-oxygen dissociation curve. The hemoglobin tetramer can bind up to four molecules of oxygen in the iron-containing sites of the heme molecules. As oxygen is bound, 2,3-BPG and CO2 a[r]

spleen. Occlusion of retinal vessels can produce hemorrhage, neovascularization, and eventual detachments. Renal papillary necrosis invariably produces isosthenuria. More widespread renal necrosis leads to renal failure in adults, a common late cause of death. Bone and joint ischemia c[r]

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 or HbC (α2β26 Glu->Lys), from the other parent. The prototype disease, sickle cell anemia,[r]

Chapter 099. Disorders of Hemoglobin (Part 7) Clinical Manifestations of Sickle Cell Trait Sickle cell trait is usually asymptomatic. Anemia and painful crises are exceedingly rare. An uncommon but highly distinctive symptom is painless hematuria often occurring in adole[r]

involve measurement of the degree to which the hemoglobin sample becomes insoluble, or gelated, as it is deoxygenated (i.e., sickle solubility test). Unstable hemoglobins are detected by their precipitation in isopropanol or after heating to 50°C. High-O2 affinity and low-O2 affinity v[r]

reflex acceleration of the heart by means of aortic and carotid reflexes, and (3) improvement of venous return to the heart by activity of the muscles of the limbs. Tilting a normal person upright on a tilt table causes some blood to accumulate in the lower limbs a[r]