Anemia: Low RBC and Hemolytic Flashcards
What are the clinical features and laboratory findings in chronic inflammation or infection (malignancy)?What is the treatment?
Dependent upon underlying disease associated: may include fever, arthralgias, arthritis and fatigue. For infection, symptoms and signs relate to the focus (e.g., pain, cough, swelling).Mild-moderate anemia (Hgb 8 -12 gm/dl). Severity proportional to underlying disease; may be normochromic/normocytic or microcytic with some hypochromia. ↓ serum Fe,↓TIBC, nl to ↑ ferritin,↓EPO for Hct,↓retic count.Treat underlying disease (infection, malignancy) to decrease cytokines and interleukins. Treat co-morbid conditions (e.g., iron deficiency). EPO has been shown to be effective in some cases
What are the clinical features and laboratory findings in lead intoxication? What is the treatment?
Personality changes, irritability, headache, weakness, wt loss, abdominal pain and vomiting presenting with insidious nature.Mild to moderate anemia.↓retic count. Microcytosis and mild hypochromia. Basophilic stippling.↑zinc protoporphyrin. May see concurrent iron deficiency confounding the diagnosis. Lead levels↑.Chelation therapy
What are the clinical features and laboratory findings in renal insufficiency?What is the treatment?
Signs and symptoms may be interrelated with those of renal dysfunction: fatigue, pallor, decreased exercise tolerance, dyspnea, tachypnea. Anemia may have other contributing factors.Usually don’t see anemia until kidney function <40% of normal. Moderate to severe anemia. Hgb 5-9 mg/dl. Normochromic, normocytic.↓retic, occasionally abnormal morphology. EPO deficiency,↓production.Administration of EPO. Treat co-morbid conditions.
What are the clinical features and laboratory findings in endocrine related anemia? What is the treatment?
Hyper or hypoactivity, weight gain or loss, systemic skin, nail, hair changes in hyper or hypothyroidism help suggest etiology. Nausea, vomiting, dehydration, weakness and circulatory collapse suggest adrenal insufficiency.Hypothyroidism: mild anemia; most normochromic, normocytic. May be microcytic or macrocytic.Hyperthyroidism: usually normocytic, may be microcytic.Adrenal: mild anemia, normocytic, all have↓reticulocyte count and index.Hormone replacement.
Identify other causes for underproduction anemia, including sideroblastic anemia, protein malnutrition, hypothyroidism, hypopituitarism, and decreased affinity hemoglobins.
Sideroblastic anemias are a heterogeneous group of disorders with deposits of iron in mitochondria of erythroid precursors.Two additional causes of underproduction anemia are hemoglobinopathies and malnutrition. Hemoglobin mutations with low oxygen affinity are associated with a right-shifted oxyhemoglobin dissociation curve, decreased oxygen affinity, normal tissue oxygen, and mild anemia because of improved oxygen delivery (in some) and/or hemolysis (depending on the specific mutation).Protein/calorie malnutrition is associated with a normochromic, normocytic anemia. There may be associated vitamin and mineral deficiencies which may also play a role in the anemia.
Describe the rationale and indications for the use of erythropoietin and transfusion in the management of underproduction anemia.
EPO is used in specific conditions where there is an absolute deficiency or where EPO levels are decreased out of proportion to the degree of anemia and administration is known to induce a response.With renal insufficiency, the lack of EPO causes anemia
Explain the biochemical basis for B12 deficiency and folate deficiency leading to a macrocytic anemia.
Folic acid and vitamin B12 (cobalamin) are critical co-factors for normal hematopoiesis.Deficiencies of folic acid and vitamin B12 profoundly affect the maturation process of red cell precursors in the marrow. The cells increase in size, arrest in S phase of mitosis, and then undergo destruction, resulting in ineffective erythropoiesis and anemia.
Identify the dietary sources of vitamin B12 and describe its associated sites and mechanisms of absorption, means of transport, and duration and location of storage.
Vitamin B12 is originally synthesized by bacteria and algae, eventually working its way up the food chain to humans through consumption of meat, eggs, and milk. It is required as a vitamin by animals but not by higher plants - hence, plants do not contribute Vitamin B12 to the diet, and a strict vegan diet can lead to deficiency.Once ingested, Vitamin B12 in food is released in the acid environment in the stomach. The protein carrier, intrinsic factor (IF), is secreted by gastric parietal cells and binds vitamin B12. In the terminal ileum, the B12 is absorbed and released from IF, bound to transcobalamin binding protein II (TcII) and transported to the liver for storage or to other tissues like the bone marrow for use.
Identify the dietary sources of folate and describe its associated sites and mechanisms of absorption, means of transport, and duration and location of storage.
Folate is widespread in food. With a typical diet, about one third of the daily folate intake is provided by cereals and bread, another one third by fruits and vegetables, and the remaining one third by meats and fish. Human milk provides enough folate for infants. Overcooking can also lead to loss of folates in food. Dietary folate is absorbed in the jejunum. It is hydrolyzed, reduced and methylated before distribution to the tissues or liver for storage (as methyltetrahydrofolate). The liver stores undergo turnover, secretion in the bile and reabsorption (enterohepatic circulation) supporting a constant supply to tissues.
Describe the findings in the peripheral blood and bone marrow in a patient with B12 or folate deficiency.
In the bone marrow, erythroid hyperplasia leading to an alteration of the myeloid:erythroid (M:E) ratio from a myeloid to an erythroid predominance is observed.In peripheral blood, the anemia is variable. There is macrocytosis (MCV >97 fl in adults). The reticulocyte count is decreased, with a reticulocyte index <1.0. On the peripheral smear, macro-ovalocytes and hyper-segmented (%4-5 lobes) neutrophils can be observed. As the anemia progresses, poikilocytes and fragmentation may be seen. In severe cases, neutropenia and thrombocytopenia can be documented, as well as increases in bilirubin and LDH levels due to intramedullary (within the bone marrow) destruction of red cells.
Describe vitamin B12 deficiency with respect to: their most common causes, time to development of the clinical state, presence of neurologic and neuropsychiatric abnormalities, and laboratory studies used to make a diagnosis.
The most common cause of Vitamin B12 deficiency is pernicious anemia, due to autoimmune destruction of IF-producing gastric parietal cells.This condition is most common in the older age population.Other causes include failure to produce IF (gastritis, gastrectomy, congenital), malabsorption (multiple disorders), defective transport or storage (TcII deficiency) and metabolic defects in pathways which utilize B12 as a substrate.Vitamin B12 deficiency takes several months to develop because of its long half-life within the body and large hepatic stores. Vitamin B12 deficiency develops more slowly and is more likely associated with malabsorption.Neurologic involvement is classic in B12 deficiency.Direct measurement of serum cobalamin levels. Measurement of plasma homocysteine levels has been used as a more sensitive marker of deficiency of B12 and folate in the tissues.
Describe folate deficiency with respect to: their most common causes, time to development of the clinical state, presence of neurologic and neuropsychiatric abnormalities, and laboratory studies used to make a diagnosis.
The most common cause of folate deficiency leading to megaloblastic anemia is inadequate dietary intake. Other causes include malabsorption due to such things as tropical sprue or parasitic infection, inborn errors of folate metabolism (very rare), and increased demands (hemolysis, pregnancy/lactation, rapid growth, psoriasis, myeloproliferative disorders), and Alcohol consumption.The onset of folate deficiency can occur quite rapidly (within weeks), particularly in the setting of malabsorption or alcoholism.Neurological symptoms are not common in folate deficiency.Direct measurement red cell folate levels is useful in diagnosing deficiencies, although there can be problems with these tests. Measurement of plasma homocysteine levels has been used as a more sensitive marker of deficiency of B12 and folate in the tissues.
Describe the clinical, laboratory, and autoimmune findings associated with pernicious anemia.
Clinical: Bleeding gums, diahhrea, fatigue, neurological symptoms, pallor, personality and memory changes, SOBLaboratory: Measurement of serum autoantibodies against intrinsic factor, the cobalamin-intrinsic factor complex, and parietal cells is now commonly used to diagnose pernicious anemia, with positivity in more than 60% of adults with the disease.Autoimmune: autoantibodies against intrinsic factor
Describe the appropriate therapies for B12 deficiency and folate deficiency.
Cobalamin deficiency: Intramuscular or subcutaneous injections of B12, with a typical schedule being daily for 2 weeks, then weekly until the hematocrit is normal, then monthly for life. If absorption is not an issue, replacement can be oral. In some cases of pernicious anemia, large oral doses given daily can overcome the absorption defect, but correction of the deficiency needs to be documented.Folate deficiency: 1 mg/day orally or parenterally.
Provide a definition for hemolysis and describe the two main mechanisms of increased destruction of RBCs, intravascular hemolysis and extravascular hemolysis.
Hemolysis is defined as a decrease in red cell survival or increase in turnover beyond standard norms.Red cells undergoing intravascular hemolysis release hemoglobin into the circulation.With extravascular hemolysis, the red cell is ingested by macrophages of the RE system. The heme is separated from globin, iron removed and stored in ferritin, and the porphyrin ring converted to bilirubin which is released from the cell.