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Reduction in total number of erythrocytes in circulating blood or a decrease in the quality or quantity of hemoglobin.
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Result from: impaired erythrocyte production; blood loss (acute or chronic); increased erythrocyte destruction; or a combination of all three
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Classified in two ways: Etiology or Morphologic: based on size (“cytic”) and hemoglobin content ( “chromic”)
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Additional descriptions of erythrocytes associated with some anemias are:
Anisocytosis ( assuming various sizes) and Poikilocytosis ( assuming various shapes)
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Other terms used to assess erythrocytes: o For Volume: Normocytic (normal) Increased Erythrocyte volume :
Macrocytic (higher mean corpuscular volume {MSV}); Decreased volume: Microcytic (lower MCV) o For Hemoglobin Content: Normochromic (normal), Hyperchromic (higher mean corpuscular hemoglobin concentration {MCHC}) Hypochromic
(lower MCHC)
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Major physiologic manifestation is reduced oxygen-carrying capacity of blood, producing tissue hypoxia.
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Initial manifestations are apparent in the cardiovascular system.
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Compensation is primarily executed by the: cardiovascular, respiratory, and hematologic systems. o For reduced blood volume: fluids move from interstitium to intravascular space (osmotic gradient), expanding plasma volume.
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Hypoxia causes systemic arterial dilation, which leads to decreased vascular resistance, which reduces afterload.
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Sympathetic nervous system is activated, causing increased heart rates.
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Other manifestations observed in: skin, mucous membranes, lips, nail beds and conjunctivae become pale. With RBC destruction (hemolysis), skin may become yellowish. Hypoxia causes impaired healing and loss of elasticity to skin, thinning and early graying of hair.
Macrocytic-Normochromic Anemia (Megaloblastic Anemia)
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Defective DNA synthesis results in ineffective erythropoiesis manifested by unusually large stem cells (megaloblasts) in marrow that mature into unusually large stem cells (macrocytes) in the circulation.
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Thickness and volume of cell also increase
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Defective DNA caused by deficiencies in: Vit. B12, folate, coenzymes required for nuclear maturation, and the DNA synthesis pathway.
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Ineffective erythropoiesis contributes to premature death of all cell lines within the bone marrow. o Types:

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Pernicious Anemia:
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most common type
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predominantly over 60 years of age, female more common
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tendency also in Blacks and Hispanics
 caused by Vit B12 deficiency
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Often associated with end stage type A chronic atrophic (autoimmune) gastritis.
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Absence of intrinsic factor
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Folate Deficiency Anemia
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Folate (folic acid): an essential vitamin required for erythrocyte production and maturation.
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Dietary intake only source: 50-200 mcg/day
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Synthesis of folate takes place in intestine with absorption in the upper small intestine
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Deficiency more common in cobalamin deficiency, commonly associated with alcoholism and other conditions causing chronic malnourishment.
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Primary biochemical function of folate coenzymes involves the synthesis of purines and pyrimidines, which form structural elements of DNA and RNA.
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Folate deficiency thought to cause apoptosis of erythroblasts in the late stages of differentiation. In addition to anemia, folate deficiency also associated with neural tube defects of the fetus and heart disease.
Also implicated in development of cancers, specifically colorectal cancer.
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Microcytic-Hypochromic Anemia o Erythrocytes abnormally small and contain abnormally reduced amounts of hemoglobin. o Result from disorders of: iron metabolism, porphyrin and heme synthesis; or globin synthesis
.
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Types o Iron Deficiency Anemia
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Most common type worldwide
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Populations at risk include: those living in chronic poverty, women of childbearing age, and children.
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Most common cause in well-developed countries is pregnancy and chronic blood loss (as little as 2-4 ml/day is sufficient to cause)
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Causes of chronic blood loss: erosive esophagitis, gastric and duodenal ulcers, colon adenomas and cancers.
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Other causes:

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H.Pylori
infections may cause due to impaired iron uptake.
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Mennorhagia
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Eating disorders, such as pica
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Insufficient dietary intake of iron
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Surgical procedures that decrease stomach acidity, intestinal transit time and absorption.
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Iron is needed for normal erythropoiesis, contributes to immune function by regulation immune effector mechanisms, nitric oxide formation, and T-cell proliferation.
 Pathogenesis of anemia is recognized as being part of the nonspecific acute phase response to any type of inflammation of sufficient degree.
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Symptoms (may not be apparent until Hgb decreased to 7-
8g/dl): Early : pale earlobes, palms and conjunctivae;
Progressive : nails become brittle and thin, coarsely ridged and spoon-shaped or concave (koilonychias) as a result of impaired circulation, glossitis (red, sore, painful, caused by atrophy of papillae), angular stomatitis (dryness and soreness in epithelium of corners of mouth), dysphagia associated with esophageal web which has potential to become malignant and is associated with malignancies of GI tract. In elderly may see mental confusion, memory loss and disorientation.
o Diagnosis : presence of decreased hemoglobin and Hematocrit. May also measure iron stores via bone marrow biopsy and iron staining.
Indirect test: serum ferritin, transferring saturation, total iron-binding capacity. o Treatment: identify and eliminate or rule out, sources of blood loss, iron replacement in nutritional deficient anemia o Sideroblastic Anemia
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Anemia characterized by deviation in mitochondrial metabolism which causes ineffective iron uptake resulting in dysfunctional hemoglobin synthesis.
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Diagnosis : ringed sideroblasts with the bone marrow
(erythroblasts that contain iron granules that have not been synthesized into hemoglobin, but are distributed in a perinuclear collar arrangement around one third or more of the nucleus).
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Symptoms : hemoglobin levels varying from 4-10g/dl, erythropoietic hemochromatosis (iron overload), spleenomegaly, and hepatomegaly. Major complications: heart rhythm disturbances, congestive heart failure.
 Treatment: Identification of causative agent (i.e., drugs or toxins), supportive (transfusions primary intervention), oral pyridoxine on a trial basis.

Normocytic-Normochromic Anemia
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Erythrocytes normal in size and hemoglobin content, insufficient in number.
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No common etiology
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Less common than other anemias
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Five distinct groups: aplastic, posthemmorhagic, hemolytic, sickle cell and anemia of chronic inflammation.
o Aplastic Anemia : pancytopenia (reduction or absence of all three blood cell types) resulting from failure or suppression of bone marrow to produce adequate amounts of blood cells; relatively rare; idiopathic acquired most common, other causes include known chemical agents and ionizing radiation. Diagnosis : bone marrow biopsy . Treatment : Bone marrow and peripheral blood stem cell transplant provides highest survival rates. o Posthemmorhagic Anemia (Acute Blood Loss): Normocyticnormochromic anemia caused by acute blood loss from the vascular space. Symptoms apparent with loss >1500 ml (even in recumbent position), loss exceeding 2000ml=severe shock, lactic acidosis and death. Treatment: restoration of blood volume by IV saline, dextran, albumin, or plasma. Large volume losses may require transfusions of fresh whole blood. o Hemolytic Anemia : premature, accelerated destruction of erythrocytes, may occur either episodically or continuous. Classified as hereditary
(intrinsic abnormality) or acquired (extrinsic or extracellular defect).
Diagnosis: evaluation of clinical manifestations, bone marrow studies and blood tests. Treatment : removing cause or treating underlying disorder. Acute fulmination hemolytic anemia (hemolytic crisis) treated with fluid and electrolyte replacement to prevent shock and renal damage, which may be caused by RBC debris clogging the kidney tubules. Transfusions and spleenectomy may be required. o Anemia of Chronic Disease : mild to moderate, chronic conditions include: AIDS, chronic inflammatory disorders, including RA, SLE, acute and chronic hepatitis, chronic renal failure, and malignancies.
Causes may include: decreased erythrocyte life span, ineffective bone marrow response to erythropoietin, and altered iron metabolism.
Diagnosis : low serum iron, low or normal total iron binding capacity
(TIBC), normal of high serum ferritin level and low concentrations of soluble transferrin receptor. Treatment: aimed at alleviating underlying disorder.
Myeloproliferative RBC Disorders (Polycythemia)
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Increase in RBC production. Two forms: relative and absolute.
o Relative : results from any cause of dehydration such as: decreased water intake, diarrhea, excessive vomiting or increased use of diuretics. Temporary, usually affects obese, hypertensive or stressed individuals, and resolves with appropriate fluid administration or treatment of underlying condition.

o Absolute : primary: results from an abnormality of the bone marrow stem cells; secondary : most common, caused by an increase in erythropoietin as a normal physiologic response to chronic hypoxia or inappropriately to erythropoietin-secreting tumors. (Individuals living at higher altitudes, smokers, COPD,
CHF). Treatment aimed at minimizing risk of thrombosis and preventing progression to myelofibrosis and acute leukemia.