Red blood cells sickled

FIGURE 19.18 Sickle-shaped red blood cells form when only one amino acid (glutamic acid) in a polypeptide chain is replaced by another amino acid (valine). These cells are less able to take up oxygen than normal cells. 

Hematological Methods. Hematological analyses can Include the determination of the total hemoglobin concentration (In g%), the packed cell volume (PCV In %), the red blood cell count (In 10 /mm ) and reticulocytes count (In %), calculation of the red cell Indices, examination of a blood film, tests to demonstrate the presence of Inclusion bodies and of sickle cells, tests to evaluate the distribution of fetal hemoglobin (Hb-F) Inside the red cells, the red cell osmotic fragility, the concentration of serum Iron (SI), total Iron binding capacity (TIBC), and the survival time of the red cells. Details of all... 

FIGURE 65-2. Elongated sickle-shaped and normal discoidshaped red blood cells. (From Chan CYJ, Moore R. Sickle cell disease. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 1856.)... 

HbSC, sickle-hemoglobin C Hgb, hemoglobin RBC, red blood cell SCA, sickle cell anemia. 

VORDERMEIER S, SlNGH S, BiGGERSTAFF J, Harrison P, Grech H, Pearson TC, Dumonde DC, Brown KA. Red blood cells from patients with sickle cell disease exhibit an increased adherence to cultured endothelium pretreated with tumour necrosis factor (TNF). Br J Haematol 1992 81 591-597. 

Sickle cell syndromes are hereditary disorders characterized by the presence of sickle hemoglobin (HbS) in red blood cells (RBCs). 

In people with sickle cell anemia, there is just one mutation in each of the P chains. The glutamic acid in position 6 is substituted by valine. This substitution, two residues out of a total of 474, is sufficient to cause the red blood cell to deform and constrict blood flow by blocking the capillaries. 

We begin with the symptoms of sickle cell anemia. As the name implies, victims are frequently anemic that is, they have a content of hemoglobin in blood less than the normal range, the result of lysis of red blood cells, the carriers of hemoglobin (hemolytic anemia). In addition, disease victims are susceptible to chronic infections, may have enlarged spleens, and suffer intermittent bouts of pain, which can be severe, in the bones, joints, and periosteum. The disease can be debilitating. 

Sickle cell anemia a genetic disease that compromises the ability of red blood cells to deliver oxygen to the tissues. 

A nonbiological reductant (8204 ) that has proven to be of immense value in converting uncomplexed and porphyrin-bound Fe(III) to the +2 oxidation state with the concomitant formation of two molecules of SO2 gas. Dithionite also reacts with heme-bound oxygen to produce deoxyhemoglobin, and treatment of intact red blood cells with dithionite can induce sickling in cells containing hemoglobin S. Dithionite also reduces NAD+ to NADH. 

Red blood cell fractions are administered to patients suflfering from severe anaemia, including patients with sickle cell anaemia and new born babies suflfering from haemolytic disease. 

Sickle-cell anemia causes red blood cells to assume a sickle shape. The abnormal blood cells disrupt blood circulation, which can lead to infections, organ damage, and chronic pain. 

The ability of NO to react at least 1000-times more rapidly with free Hb than with Hb in red blood cells may have important implications for sickle-cell patients, who have increased levels of free Hb in their blood. The EPR examination of blood taken from such patients following the inhalation of NO has revealed elevated levels of Hb-Fe(III) compared with controls. Elevated free haem levels in the patients were associated with decreased NO bioavailability during the infusion of the NO donor nitroprusside, resulting in decreased blood flow.71... 

Although functioning proteins have very specific amino acid sequences, slight variations can often be tolerated. In some cases, however, a slight variation can be disastrous. For example, some people have a version of hemoglobin—a protein found in red blood cells—that has one incorrect amino acid in about 300. That minor error is responsible for sickle-cell anemia, an inherited condition with painful and often lethal effects. The sickle shape characteristic of this disease is shown in Figure 13.19. 

On the left is a red blood cell containing the normal hemoglobin protein. On the right, a sick-led red blood cell containing hemoglobin that has one out-of-place amino acid. The curved shape is reminiscent of the curved-blade harvesting tool known as a sickle. 

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