Analisis Poema A Un Olmo Seco

Introduction

Approximately one third of the mass of a mammalian red blood cell is hemoglobin. Its major function is to carry oxygen from the lungs through the arteries to the tissues and help to carry carbon dioxide through the veins back to the lungs. The process whereby hemoglobin performs this essential physiological role is characterized by a cooperative interaction among its constituent subunits. Hemoglobin has thus assumed the role of a model system whose study acquires ramifications extending far beyond its own function as an oxygen transport system.

The discovery that sickle hemoglobin has an abnormal electrophoretic mobility began the era of molecular medicine (Pauling p.110). With the advent of recombinant DNA technology, research on hemoglobin provided early and important information about the organization and regulation of genes as well as insights as to how ontogeny affects gene expression. (Schechter p.112).

Hemoglobin motifs can be found in the most ancient unicellular plants and animals and have evolved over hundreds of millions of years into gas transport proteins through the processes of gene duplication, conversion, divergence, and inactivating mutation that have culminated in hemoglobin gene clusters on separate chromosomes, whose expression is developmentally-regulated (Hardison p.201). All human hemoglobin genes contain 3 exons separated by 2 introns; the exons may encode distinct functional domains of the molecule. The tetrameric globular structure of hemoglobin is adapted to the physiology of complex organisms and their needs for regulation of oxygen delivery far better than primitive globins like hemocyanin or erythrocruorin, and single chain globins like muscle myoglobin or the other cellular globins such as cytoglobin and neuroglobin. (p.1098).

The primary amino acid structure of the constituent globin chains dictates the quaternary structure, which, in turn, is the basis of the ability of hemoglobin to rapidly bind oxygen in the lungs and unload it in the tissues. Hemoglobin function may be altered by mutation, pH, and 2, 3-biphosphoglycerate (2, 3-BPG, also called 2, 3-diphosphoglycerate or 2, 3-DPG) (p.1099).

The normal adult Hb molecule (HbA) consists of two parts of polypeptide chains designated ἁ and ß. Fetal Hb (Hb F, in which Gamma chains replace B chains) gradually decreases in the first months of life until makes up < 2 % of total Hb in adults (Merck p.878)

The types of chains and the chemical structure of polypeptides in the chains are controlled genetically. Defects may result in Hb molecules with abnormal physical or chemical properties, some results in anemias that are severes in homozygotes but mild in heterozygotes.Some patients may be heterozygous for two such abnormalities and have anemia with characteristics of both traits.

Abnormal Hbs, distinguished by electrophoretic mobility, are alphabetically designated in order of discovery (eg, A, B, C), although the first, sickle cell Hb, was designated Hb S.

Normal red blood cells.

Sickle red blood cells.

Sickle cell diseases (Hb S Disease, Drepanocytic Anemia, and Meniscocytosis): is a chronic hemolytic anemia occurring almost exclusively in blacks and characterized by sickle-shaped RBCs caused by homozygous inheritance of HbS (p.880).

Etiology.

In Hbs, valine is substituted for glutamic acid in the sixth amino acid of the ß-globin chain. This decreases its electrical charges, and it moves toward the anode more slowly than Hb A, on electrophoresis. Deoxy-Hb S is much less soluble than deoxy-Hb A; it forms a semisolid gel (polymerization) of rodlike tactoids that cause RBCs to sickle at sites of low PO2. Distorted, inflexible RBCs adhere to vascular endothelium and plug small arterioles and capillaries, which leads to occlusion and infarction Because sickled RBCs are too fragile to withstand the mechanical trauma of circulation, hemolysis occurs after they enter the circulation. (p.878)

Diagnosis.

Symptoms: in homozygotes (Hb SS), the major symptoms are anemia and vaso-occlusive events resulting in tissue ischemia and infarction, periodic joint and limb pain and sometimes edema of the joints, chronic ulceration about the ankles, episodes of severe abdominal pain with vomiting, and abdominal distention, headache is a common symptom too. Susceptibility to infection increases. Bone infarctions produce pain crisis, the most common symptom complex in Hb SS, SA and SC states .Severe abdominal pain with vomiting may simulate severe abdominal disorders.

Capillary thrombi result from sickle cells blocking small vessels and may cause vaso-occlusive (painful) crisis and hand-foot syndrome (swelling) in children.

Increased concentration (dehydration) makes symptomps worse; decreased concentration (with thalassemia) makes symptoms better.

Decreased pH decreases oxygen affinity and makes symptoms worse.

Increased hemoglobin F makes symptoms better (rationale for therapy with hydroxyurea, which increased blood hemoglobin F levels).

Presence of hemoglobin C (SC: double heterozygote individual makes symptoms better.

Signs: Pallor, mild jaundice, hepatoesplenomegaly, growth and development are impaired, patients often have short trunk with long extremities and a tower- shaped skull. Chronic marrow hyperactivity causes typical bone changes, seen on x-ray: widening of the diploic spaces of the skull and the sunray appearance of the diploic trabeculations are characteristics. The long bones often show cortical thinning, irregular densities, and new bone formation within the medullary canal. (p.879)

The spleen in adults is commonly very small due to “autoesplenectomy”, Howell-Jolly bodies will appear in peripheral blood after autosplenectomy and results in increased incidence of infections (encapsulated organisms), cardiomegaly is usual and cholelitiasis is common. Paralysis and convulsions may result from cerebral thrombosis, which can cause stroke, blindness, and other neurological disturbances. There is a tendency toward progressive renal disease and renal failure. (Med. 2007)

Acute chest syndrome is the major cause of death in patients > 5 yr. It occurs in all age groups, but the frecuency decreases in adulthood. It is characterized by sudden onset of fever, chest pain, leukocytosis, and pulmonary parenchymal infiltrates on chest x- ray. Priapism is an emergency too.

Heterozygotes (Hb AS) are normal and do not experience hemolysis painful crises, or thrombotic complications. An increased incidence of rhabdomyolisis and sudden

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