Blood cell deficiencies, anemias

Different classifications of anemia are based in part on the pathophysiological factor inducing the decreased hemoglobin concentration. Anemias due to cell hy-poproliferation include aplastic anemia and iron deficiency anemia. Hemolytic anemia results from excessive destruction of red blood cells. Megaloblastic anemia, sideroblastic anemia, and iron deficiency anemia result from an abnormality in the maturation of red blood cells. 

A. Iron and Vitamin Deficiency Anemias Microcytic hypochromic anemia, caused by iron deficiency, is the most common type of anemia. Megaloblastic anemias are caused by a deficiency of vitamin B, or folic acid, cofactors required for the normal maturation of red blood cells. Pernicious anemia, the most common type of vitamin Bj, deficiency anemia, is caused by a defect in the synthesis of intrinsic factor, a protein required for efficient absorption of dietary vitamin B 2, or by surgical removal of that part of the stomach that secretes intrinsic factor. 

Figure 33-1. Drugs used in the treatment of anemias and blood cell deficiencies. G-CSF, granulocyte colony-stimulating factor GM-CSF, granulocyte-macrophage colony-stimulating factor IL-11, interleukin-11.

V.B12 is also known as antipemicious anemia factor. Pernicious anemia is characterized by a severely reduced production of red blood cells, deficient gastric secretion and disturbances of the nervous system. It is not usually caused by dietary deficiency of V.B]2, but by the absence of intrirrsic factor, which is required for V.B[2 absorption. Intrinsic factor is a neuraminic acid-containing glycoprotein, normally present in the gastric mucosa, which forms a pepsin-resistant complex with V.B,2, and enables V.B,2 absorption in the lower part of the intestinal traet. 

Cobalamin is the anti-pernicious anemia factor. Minutest amounts (a few micrograms) cure pernicious anemia in man. The disease is characterized by a drastic decrease of the erythrocyte count (due to a disturbance in the maturation of red blood cells). Pernicious anemia does not arise from a dietary deficiency, but rather is caused by a defect in the absorption of the vitamin. Cobalamin (designated the extrinsic factor, in this connection) can be taken up by the human organism only in the presence of the intrinsic factor, a mucoprotein. The latter is formed in the gastric mucosa its absence causes pernicious anemia. 

Anemia is defined by abnormally low circulating hemoglobin concentrations. A variety of etiologies exist for anemia, including dietary deficiencies of folate or vitamin B12 (pernicious or macrocytic anemia), infections and inflammatory states (anemia of chronic disease), and conditions that result in insufficient production of red blood cells (aplastic anemia) or excessive destruction of red blood cells (hemolytic anemia). However, worldwide, the most prevalent form of anemia is that of iron deficiency, which causes anemia characterized by hypochromic and normo- or microcytic red blood cells. Iron deficiency anemia remains a health problem in both the developed and the developing world. This article discusses the metabolism of iron the assessment of iron deficiency iron requirements across the life span and the consequences, prevention, and treatment of iron deficiency and iron deficiency anemia. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

The symptoms of vitamin E deficiency in animals are numerous and vary from species to species (13). Although the deficiency of the vitamin can affect different tissue types such as reproductive, gastrointestinal, vascular, neural, hepatic, and optic in a variety of species such as pigs, rats, mice, dogs, cats, chickens, turkeys, monkeys, and sheep, it is generally found that necrotizing myopathy is relatively common to most species. In humans, vitamin E deficiency can result from poor fat absorption in adults and children. Infants, especially those with low birth weights, typically have a vitamin E deficiency which can easily be corrected by supplements. This deficiency can lead to symptoms such as hemolytic anemia, reduction in red blood cell lifetimes, retinopathy, and neuromuscular disorders. 

Aplastic anemia—anemia due to deficient red blood cell production in the bone marrow... 

Anemia is a decrease in the number of red blood cells (RBCs), a decrease in die amount of hemoglobin in RBCs, or bodi a decrease in die number of RBCs and hemoglobin. When diere is an insufficient amount of hemoglobin to deliver oxygen to die tissues, anemia exists. There are various types and causes of anemia For example, anemia can be die result of blood loss, excessive destruction of RBCs, inadequate production of RBCs, and deficits in various nutrients, such as in iron deficiency anemia Once the type and cause have been identified, die primary health care provider selects a method of treatment. 

Vitamin B12 is essential to growth, cell reproduction, the manufacture of myelin (which surrounds some nerve fibers), and blood cell manufacture. The intrinsic factor, which is produced by cells in the stomach, is necessary for the absorption of vitamin B12 in the intestine A deficiency of the intrinsic factor results in abnormal formation of erythrocytes because of the body s failure to absorb vitamin B12, a necessary component for blood cell formation. The resulting anemia is a type of megaloblastic anemia called pernicious anemia. 

Anemias, reductions in the number of red blood cells or of hemoglobin in the blood, can reflect impaired synthesis of hemoglobin (eg, in iron deficiency Chapter 51) or impaired production of erythrocytes (eg, in folic acid or vitamin Bjj deficiency Chapter 45). Diagnosis of anemias begins with spectroscopic measurement of blood hemoglobin levels. 

Current NKF guidelines define anemia as a hemoglobin (Hgb) level less than 11 g/dL (6.8 mmol/L).31 A number of factors can contribute to the development of anemia, including deficiencies in vitamin B12 or folate, hemolysis, bleeding, or bone marrow suppression. Many of these can be detected by alterations in RBC indices, which should be included in the evaluation for anemia. A complete blood cell count is also helpful in evaluating anemia to determine overall bone marrow function. 

Anemia of chronic kidney disease A decline in red blood cell production caused by a decrease in erythropoietin production by the progenitor cells of the kidney. As kidney function declines in chronic kidney disease, erythropoietin production also declines, resulting in decreased red blood cell production. Other contributing factors include iron deficiency and decreased red blood cell lifespan, caused by uremia. 

Hereditary Hemolytic Anemia Associated with Red Blood Cell Enzyme Deficiency. 14... 

Hexokinase (Hx) deficiency in red blood cells is a rare disease in which the predominant clinical effect is chronic nonspherocytic hemolytic anemia. After the... 

Hereditary deficiency of phosphoglycerate kinase (PGK) is associated with hereditary hemolytic anemia and often with central nervous system dysfunction and/or myopathy. The first case, reported by Kraus et al. (K24), is a heterozygous female, and the results are not so clear. The second family, reported by Valentine et al. (V3), is a large Chinese family, whose pedigree study indicates that PGK deficiency is compatible with X-linked inheritance. To date, 22 families have been reported (04, T25, Y3). Nine of these have manifested both symptoms five have shown only hemolysis seven have shown the central nervous system dysfunction and/or myopathy but without hemolysis and one case, PGK Munchen, is without clinical symptoms (F5). PGK II is an electrophoretic variant found in New Guinea populations (Y2). Red blood cell enzyme activity, specific activity, and the kinetic properties of this polymorphic variant are normal. 

Deficiency of GC-S is extremely rare only five cases from four unrelated families have been reported so far (B18, HI7, K23). This enzyme deficiency appears to be inherited as an autosomal recessive and has been clearly associated with a moderate chronic hemolytic anemia and a marked decrement of red blood cell GSH. Spinocerebellar degeneration and aminoaciduria were present in both homozygous siblings in the first family, whereas no neurologic deficit was noted in the other three families. 

GSH-S deficiency is a more frequent cause of GSH deficiency (HI7), and more than 20 families with this enzyme deficiency have been reported since the first report by Oort et al. (05). There are two distinct types of GSH-S deficiency with different clinical pictures. In the red blood cell type, the enzyme defect is limited to red blood cells and the only clinical presentation is mild hemolysis. In the generalized type, the deficiency is also found in tissues other than red blood cells, and the patients show not only chronic hemolytic anemia but also metabolic acidosis with marked 5-oxoprolinuria and neurologic manifestations including mental retardation. The precise mechanism of these two different phenotypes remains to be elucidated, because the existence of tissue-specific isozymes is not clear. Seven mutations at the GSH-S locus on six alleles—four missense mutations, two deletions, and one splice site mutation—have been identified (S14). 

Pyrimidine 5 -nucleotidase (P5N) deficiency appears to be the third most common cause of hereditary nonspherocytic hemolytic anemia after G6PD and PK deficiencies. To date, more than 42 cases have been reported worldwide (FI 1) since the first report by Valentine et al. (V4). This syndrome is characterized by hemolytic anemia, pronounced basophilic stippling of red blood cells (Fig. 6), and a... 

H17. Hirono, A., Iyori, H., Sekine,I.,Ueyama, J., Chiba, H., Kanno, H., Fujii, H and Miwa, S., Three cases of hereditary nonspherocytic hemolytic anemia associated with red blood cell glutathione deficiency. Blood 87,2071-2074 (1996). 

The primary cause of anemia in patients with CKD or ESRD is erythropoietin deficiency. Other contributing factors include decreased lifespan of red blood cells, blood loss, and iron deficiency. 

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