Erythrocytes Haemolysis

Vitamin E deficiency is normally associated with diseases of fat malabsorption and is rare in humans. Deficiency is characterized by erythrocyte haemolysis and prolonged deficiency can cause neuromuscular dysfunction. Hypervitaminosis E is not common, despite an increased intake of vitamin E supplements. Extremely high doses of the vitamin may interfere with the blood clotting process. 

The physiological role of vitamin K is in blood clotting and is essential for the synthesis of at least four of the proteins (including prothrombin) involved in this process. Vitamin K also plays a role in the synthesis of a protein (osteocalcin) in bone. Vitamin K deficiency is rare but can result from impaired absorption of fat. Vitamin K levels in the body are also reduced if the intestinal flora is killed (e.g. by antibiotics). Vitamin K toxicity is rare but can be caused by excessive intake of vitamin K supplements. Symptoms include erythrocyte haemolysis, jaundice, brain damage and reduced effectiveness of anticoagulants. 

The blood cell toxins have a specific effect upon only one blood cell, the red blood cell (RBC) or erythrocyte. They cause the rupture of erythrocytes (haemolysis). This is clearly a very undesirable eventuality, which in its own right would result in death. However it is difficult to decide whether this property of several of the snake toxins is particularly important from the point of view of their fatality potential, because it is slow and it is very likely that one of the other toxins in the venom would have killed the unfortimate recipient before the haemolytic toxin had a chance to exert its effect. 

The antioxidant effect of different types of lignins has been evaluated by their capacity to inhibit human erythrocyte haemolysis induced by AAPH [2,2 -az-obis(2-amidopropane) dihydrochloride], a peroxyl radical initiator (Fig. 8.10) [150], or by hydrogen peroxide [151]. 

Comparative studies In a 4-month double-blind, randomised trial involving 180 healthy subjects, the ability of vitamin E supplementation to protect erythrocyte membranes from oxidative stress was examined. Vitamin E supplementation was associated with a significant decrease in erythrocyte haemolysis (p<0.05). None of the participants experienced any adverse effects with vitamin E supplementation... 

Red blood cell (RBC) Mammalian erythrocytes Haemolysis, denaturation of oxyhaemoglobin Optimised vahdation... 

Penetration of the biomembrane is undoubtedly essential for most membrane activity. Araki and Rifkind (13) obtained esr spectra of stearic acid spin labelled erythrocyte membranes in the presence of diverse compounds including Triton XlOO, chlorpromazine and glutaraldehyde. The two surfactants chlorpromazine and Triton XlOO both increase the rate of haemolysis and are shown to increase membrane fluidity. Glutaraldehyde as expected decreases fluidity and decreases the rate of haemolysis. 

The NADPH is produced from glucose 6-phosphate in the first three reactions in the pentose phosphate pathway (see below). Hence the pentose phosphate pathway is essential in the erythrocyte and glycolysis provides the substrate glucose 6-phosphate. Individuals with a reduced amount of glucose 6-phosphate dehydrogenase can suffer from oxidative damage to their cells and hence haemolysis. 

Administration of this silatrane, especially at 0.01% concentration, to the erythrocytes incubated with thallium nitrate increases their resistance to haemolysis. The erythrograms shift to the right and the maximum erythrocytolysis decreases to 25% whereas the resistance time amounts to 600 30 sec (Fig. 6). 

On administration of 0.1 and 0.01% of l-(0,0-diethylphosphonemethyl)-3,7,10-trimethylsilatrane in physiologic saline solution to the blood of animals poisoned with lead nitrate a sharp increase in acid resistance of erythrocytes was oberved (Fig. 7) along with erythrogram shift to the right and a prolonged prelytic time (to 240 60 sec). Sometimes the maximum erythrocytolysis occurs only after 300 60 sec. Haemolysis is completed in 720 30 sec. 

Observations on deficiency symptoms in the cardiovascular system were also made [29, 30]. In chicks, exudative diathesis, a condition in which plasma moves from the capillaries into surrounding, particularly subcutaneous, tissue, was studied and found to be associated with lipid peroxidation [31]. In cardiac muscle, a necrotizing myopathy was found in vitamin-E-deficient mice [32], rats [33], rabbits [34] and ruminants [35], Blood abnormalities, associated with increased susceptibility of erythrocytes to haemolysis, figure among reports of the effects of vitamin E deficiency [36, 37]. 

In 1979, Jette E. Kristiansen of Copenhagen, Denmark, performed extensive experiments to elaborate the effect of chlorpromazine on the permeability of the bacterial cell wall [55]. In vitro experiments were carried out with Staphylococcus aureus under the influence of chlorpromazine. Depigmentation and bacteriostatic/bactericidal effects of chlorpromazine on the microorganisms were observed. It has been shown that concentrations of chlorpromazine near the bacteriostatic value, in combination with bacterial haemolysins, could alter erythrocyte membranes of horse and rabbit blood in such a way that they become resistant to haemolysis. It was further realized that chlorpromazine in bacteriostatic concentration probably changed the transport of potassium through the bacterial membrane in the same manner as described for mammalian muscle tissue [54],... 

Bilirubin Produced from haemoglobin during degradation of erythrocytes. Found in bile 5-21 pmol/L Raised in hepatocyte dysfunction, biliary obstruction and haemolysis... 

Type II reactions are mimicked by the haemolysis induced by drugs (some antimalarials, sulpho-namides and oxidising agents) and food (broad beans) in subjects with inherited abnormahties of erythrocyte enzymes or haemoglobin (see p. 123). 

The determination of ammonia in blood is carried out enzymatically, which is considered to be specific, precise and simple. (48) Serious mistakes can easily occur during the preanalytical phase of ammonia determination, making it imperative to comply with the standardized method of taking a blood sample, (s. p. 91) EDTA blood should be taken with the addition of sodium borate and L-serine. Furthermore, elevated serum y-GT activity and increased thrombocytes cause the ammonia level to rise, as does cigarette smoking prior to blood collection. Even minor haemolysis (e. g. in the event of prolonged transport) will spoil the blood for ammonia determination, since the ammonia concentration of erythrocytes is three times that found in plasma. Besides these interfering factors, ammonia concentration is influenced by (7.) the metabolic performance of the urea cycle, (2.) the extrahepatic formation and elimination of ammonia, and (5.) the acid-base status. 

Apart from the multicausal facets involved in the haemolytic syndrome or the disorders leading to haemolysis (e.g. erythrocyte defects, toxins, noxae, antibody-mediated or mechanical factors), other causes of prehepatic jaundice are worthy of mention ... 

Pulmonary infarction jaundice following extensive haemorrhagic pulmonary infarction with haemolysis of the erythrocytes which have passed into the alveoli. 

Blood transfusions Haemolysis is due to the shortened lifespan of transfused erythrocytes. 

Vitamin E plays an important role in cell metabolism as an antioxidant for the elimination of reactive oxygen intermediates. Subsequent to intestinal resorption, vitamin E is transported in chylomicrons into the liver, from where it reaches other organs together with VLDL. Vitamin E deficiency is observed in chronic liver diseases caused by alcohol, Wilson s disease, haemochromatosis and abetalipoproteinaemia. In vitamin E deficiency, neurologic disturbances (areflexia, dysbasia, ocular palsy, reduced perception of vibration) occur haemolysis can likewise be induced or become more pronounced due to epoxide formation of unsaturated fatty acids within the erythrocyte membranes. 

Young JD, Crowley C, Tucker EM. 1981. Haemolysis of normal and glutathione-deficient sheep erythrocytes by selenite and tellurite. Biochem Pharmacol 30 2527-2530. 

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