Term
|
Definition
| formation of blood or of blood cells in the living body |
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Term
|
Definition
| production of red blood cells (as from the bone marrow) |
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Term
|
Definition
| formation of lymphocytes or lymphatic tissue |
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Term
|
Definition
| formation of blood granulocytes typically in the bone marrow |
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Term
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Definition
| process of formation of thrombocytes, usually in the bone marrow. |
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Term
| Pluripotent Hematopoietic Stem Cell (PHSC) |
|
Definition
| capable of both self-renewal and differentiation into a progenitor cell for one of the two major developmental pathways leading to the various structurally and functionally distinct end-stage, circulating cells. |
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Term
|
Definition
| Committed Stem Cell; lymphoid stem cell (LSU), myeloid stem cell |
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Term
|
Definition
| nuclear event, consists of the loss of genetic potential through the sequential inactivation of specific genes. |
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Term
|
Definition
| Cytoplasmic event; remaining genes (after differentiation) that are expressed give rise to mRNA coding for the synthesis of cellular proteins that eventually give the cells their distinct appearance and functional capabilities. |
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Term
|
Definition
| making identical copies of itself to maintain the stem cell pool |
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Term
|
Definition
1 a : rapid and repeated production of new parts or of offspring (as in a mass of cells by a rapid succession of cell divisions) b : a growth so formed
2 : the action, process, or result of increasing by or as if by proliferation |
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Term
|
Definition
|
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Term
|
Definition
| an immature red blood cell that appears especially during regeneration of lost blood and that has a fine basophilic reticulum formed of the remains of ribosomes |
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Term
|
Definition
| The quality of being polychromatic. Red cells showing a blue or lilac color are termed to be polychromatic (showing many colors). Young red cells released into the peripheral blood as a consequence of increased production are larger than mature erythrocytes and more basophilic on staining. |
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Term
|
Definition
| an erythrocyte that is normal in size, shape and color. |
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Term
|
Definition
| a glycoprotein hormone secreted by the kidney in the adult and by the liver in the fetus, which acts on stem cells of the bone marrow to stimulate red blood cell production (erythropoiesis). |
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Term
|
Definition
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Term
|
Definition
| Hb F; that forming more than half of the hemoglobin of the fetus, present in minimal amounts in adults and abnormally elevated in certain blood disorders. |
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Term
|
Definition
| Hb Gower 1, Hb Gower 2, Hb Portland |
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Term
|
Definition
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Term
|
Definition
| A beta globulin in blood serum that combines with and transports iron. Also called siderophilin. A protein in blood plasma that carries iron derived from ood intake to the liver, spleen, and bone marrow. |
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Term
|
Definition
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Term
|
Definition
| Responsible for regulation of Fe storage and tissue transport to plasma, found in the reticuloendothelial cells of the intesting, liver, spleen, bone marrow and hepatocytes. |
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Term
|
Definition
| aggregared/phagocytized form of ferritin. degraded ferritin, and can appear as an abnormal microscopic pigment found in the human body. Hemosiderin is composed of iron oxide and can accumulate in different organs in various diseases. |
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Term
|
Definition
| medical laboratory test that measures the amount of circulating iron that is bound to transferrin. |
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Term
| Total Iron Binding Capacity (TIBC) |
|
Definition
| medical laboratory test which measures the extent to which iron-binding sites in the serum can be saturated. Taken together with serum iron and percent transferrin saturation clinicians usually perform this test when they are concerned about anemia, iron deficiency or iron deficiency anemia. However, because the liver produces transferrin, liver function must be considered when performing this test. It can also be an indirect test of liver function, but is rarely used for this purpose. |
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Term
|
Definition
| a group of inherited or acquired disorders of certain enzymes in the heme biosynthetic pathway. classified as acute (hepatic) porphyrias and cutaneous (erythropoietic) porphyrias, based on the site of the overproduction and accumulation of the porphyrins (or their chemical precursors). They manifest with either skin problems or with neurological complications (or occasionally both). A clinically and histologically identical condition is called pseudoporphyria. Pseudoporphyria is characterized by normal serum and urine porphyrin levels. |
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Term
|
Definition
| α thalassemias involve the genes HBA1 and HBA2. inherited in Mendelian recessive fashion. Connected to the deletion of the 16p chromosome. result in decreased alpha-globin production, therefore fewer alpha-globin chains are produced, resulting in an excess of β chains in adults and excess γ chains in newborns. The excess β chains form unstable tetramers (called Hemoglobin H or HbH of 4 beta chains) which have abnormal oxygen dissociation curves. |
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Term
|
Definition
| Beta thalassemias are due to mutations in the HBB gene on chromosome 11. inherited in an autosomal-recessive fashion. Mutations are characterized as (βo) if they prevent any formation of β chains; they are characterized as (β+) if they allow some β chain formation to occur. In either case there is a relative excess of α chains, but these do not form tetramers: rather, they bind to the red blood cell membranes, producing membrane damage, and at high concentrations they form toxic aggregates. |
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Term
|
Definition
| kind of genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. Common haemoglobinopathies include sickle-cell disease and thalassemia. It is estimated that 7% of worlds population (420 million) are carriers, with 60% of total and 70% pathological being in Africa. Hemoglobinopathies are most common in ethnic populations from Africa, the Mediterranean basin and Southeast Asia. |
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Term
Colony forming unit
(CFU-S) |
|
Definition
| a cell that, if injected into an irradiated host animal, would give rise to colonies in the spleen that contain all the precursors for erythrocytes, granulocytes, monocytes, and megakaryocytes. |
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|
Term
Colony Forming Unit
(CFU-GM) |
|
Definition
| Colony forming unit that would give rise to splenic or hepatic colonies of cells containing recognizable precursors of granulocytes and monocytes (GM) |
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Term
|
Definition
| Colony Forming Unit that would produce in an irradiated host animal, splenic and hepatic colonies of more completely differentiated cell types in the erythrocyte developmental series |
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Term
|
Definition
Reduction in red cell mass (RBC/MM3)
reduction in hemoglobin or hematocrit (Hgb/Hct or H/H)
H/H below level for adequate tissue oxygenation
Not a disease by itself but is an objective sign of a disease |
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Term
Anemia Pathogenesis
(Dr. Henschke) |
|
Definition
| Microcytic- Iron Deficiency; Macrocytic (AKA Megaloblastic)- B12 or Folate deficiencyy; Normocytic/Normochromic- anemia of chronic disease; Mixed/Multifactorial/Dimorphic- combination of 2 or more types |
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Term
Types of Anemia by pathophysiology
(Dr. Henschke) |
|
Definition
| Nutritional deficiencies (vitamin), acute diseases (GI bleed or trauma), chronic diseases (renal failure), drug induced (G6PD or immune), decreased red cell production (stem cell differentiation), increased red cell destruction (hemolysis, G6PD or sickle cell), increased red cell loss (chronic bleed) |
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Term
Anemia- most common causes
(Dr. Henschke) |
|
Definition
acute blood loss (GI bleed, traumatic bleed, AAA rupture)
Iron deficiency (Subacute)
Chronic disease (renal, liver, infection, inflammatory, granulomatous, collagen vascular and others)
75% of all anemias |
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Term
|
Definition
| pallor of skin, mucous membrane, conjunctiva, nail beds and palmar creases (Hgb<8mb/dL); tachycardia (HR>100); heart murmurs (hyper-dynamic); angina pectoris (ischemic chest pain); exertional dyspnea (exercised induced SOB; smooth, sore, beefy red tongue; cheilosis (dry, scaling, fissuring of lips); Koilonychia (spoon-shaped nails); Fatigue and malaise |
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Term
Anemia S&S continued
(Dr. Henschke) |
|
Definition
| Postural hypotension (hypovolemia); ataxia, loss of position and vibratory sense and hyper-reflexia in B12 deficiency (demyelinating features); Jaundice (bilirubin release in hemolytic anemia); guiac and stool (blood in stool with GI blood loss); Pagophagia (ice) dirt, clay or paint pica. |
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Term
Anemia Lab Eval
(Dr. Henschke) |
|
Definition
CBC is cornerstone
Hgb, Hct, RBC count
Red cell indicates: MCV (HCT/RBC) MCH (Hgb/RBC), MCHC (Hgb/HCT)
WBC
Platelet count |
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|
Term
Anemia Lab Eval Cont.
(Dr Henschke) |
|
Definition
| Reticulocyte count; bilirubin, LDH and Haptoglobin (Alpha-2 globulin); Iron, TIBC, Ferritin, Transferring Saturation Ratio; Peripheral blood smear examination for red cell morphology; stool examination for occult blood; bone marrow aspiration and biopsy if needed. |
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Term
Iron Deficiency Anemia
(Dr. Henschke) |
|
Definition
| a state of negative iron balance (intake and stores< RBC and body demands) |
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Term
Body stores of iron
(Dr. Henschke) |
|
Definition
| Body contains 3.5g iron; 2.5g found in Hb with the remainder in Ferritin (Fe/protein- Ferric/apoferritin complex contining 23% Fe) and hemosiderin. |
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Term
|
Definition
| 0.5-1mg/day lost from urine, sweat and intestinal mucosa as ferritin; 0.5-1mg/day lost with menstruation; 1-2mg/day lost as lactoferrin in pregnancy and laction- requires supplementation beyond diet. |
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Term
Iron requirements/intake
(Dr. Henschke) |
|
Definition
| normal iron stores absorb 10% ingested dietary Fe (iron deficiency--> 20-30% absorption); av American diet 6mg Fe/1000kcal- more than enough to replace 1mg lost/day given 10% absorption; 20mg/day required for menstruating, pregnant or lactating females |
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Term
|
Definition
| Fe+2 form binds to transferrin for its journey to the reticuloendothelial system |
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Term
|
Definition
| Fe+3 form bound to storage protein apoferritin forming ferritin in reticuloendothelium |
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|
Term
Indications for parenteral iron therapy
(Dr. Henschke) |
|
Definition
| failure to respond to oral therapy (recheck for misdiagnosis- anemia of chronic ds, ongoing blood loss), intolerance to oral therapy, requires significant antacid or acid suppressive therapy, noncompliance, malabsoprtion (sprue, radiation enteritis, upper small bowel resection) |
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Term
|
Definition
| Iron dextran for injection USP- Iron as a complex of ferric hydroxide and dextran packaged as a colloidal solution containing 50mg/ml of iron. IM undiluted via Z-track to avoid staining of the skin, upper outer quadrant of buttocks, 60% absorbed in 72 hours with the remainder absorbed over weeks to months, contains dextran- assoc. w/respiratory, CNS and circulatory failure |
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|
Term
Dosage calculation for Fe deficiency anemia
(Dr. Henschke) |
|
Definition
Dose(mL)= 0.0442[Desired Hgb(g/dl)-Observed Hgb(g/dl)]*LBW(kg)+[0.26*LBW(kg)]
LBW (Male)= 50kg for first 5 ft+2.3kg for every inch over 5 feet
LBW (Female)= 45kg for first 5ft+2.3kg for every inch over 5 feet |
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|
Term
|
Definition
Male= 50kg+2.3kg for every inch over 5 feet
Female= 45kg+2.3kg for every inch over 5 feet |
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|
Term
Parenteral Iron Therapy Adverse Effects
(Dr. Henschke) |
|
Definition
| 1-2% delayed reaction in 24 to 48 hours possible lasting 3-7 days, especially with larger doses than recommended, arthralgia, dizziness, fever, HA, myalgia, nausea, chills, backache |
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Term
|
Definition
| Sodium Ferric Gluconate Complex, 12.5mg/ml (62.5/5ml) elemental iron, indicated for tx of iron deficiency anemia in patients undergoing hemodialysis and who are receiving supplemental epoetin therapy. |
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Term
|
Definition
| Iron Surcose injection as an alernate to Ferrlicit. |
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|
Term
Megaloblastic Anemia etiology
(Dr. Henschke) |
|
Definition
| B12 deficiency, folate deficiency |
|
|
Term
Megaloblastic Anemia
(Dr. Henschke) |
|
Definition
| results in large immature (AKA megaloblastic) cells from impaired DNA synthesis. |
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Term
Megalobasltic anemia potential associated features
(Dr. Henschke) |
|
Definition
| anisocytosis, poikilocytosis, elevated bilirubin, thrombocytopenia, leukopenia, hyper-segmented neutrophil nuclei |
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Term
|
Definition
| variation in size of RBC erythroid |
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Term
|
Definition
| variation in shape of RBC erythroid |
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|
Term
Megaloblastic Anemia bone marrow
(Dr. Henschke) |
|
Definition
| bone marrow will show hypercellularity and increased iron stores based on intramedullary hemolysis (R/O myeodysplastic syndrome/MDS or hematologic malignancy) |
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|
Term
Megaloblastic Anemia symptoms
(Dr. Henschke) |
|
Definition
| fatigue, exaggerated CV problems, exaggerated pulmonary problems, sore, smooth tongue, CNS effects (myelin maintenance) |
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Term
|
Definition
| oxygen-carrying pigment of erythrocytes, formed by developing erythrocytes in the bone marrow; a hemoprotein made up of four different polypeptide globin chains that contain between 141 and 146 amino acids. Hemoglobin A is normal adult hemoglobin and hemoglobin F is fetal hemoglobin. Many abnormal hemoglobins have been reported; the first were given capital letters such as hemoglobin E, H, M, and S, and later ones have been named for the place of discovery. Homozygosity for hemoglobin S results in sickle cell anemia, heterozygosity in sickle cell trait. Symbol Hb. |
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|
Term
| Mean corpuscular hemoglobin (MCH) |
|
Definition
| average hemoglobin content of an erythrocyte |
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Term
|
Definition
|
|
Term
|
Definition
| the most common abnormal hemoglobin, with valine subsituted for glutamic acid at position six of the beta change, resulting in the abnormal erythrocytes called sickle cells, and causing sickle cell anemia. |
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Term
|
Definition
| inherited autosomal recessive blood disease. In thalassemia, the genetic defect results in reduced rate of synthesis of one of the globin chains that make up hemoglobin. Reduced synthesis of one of the globin chains can cause the formation of abnormal hemoglobin molecules, and this in turn causes the anemia which is the characteristic presenting symptom of the thalassemias. |
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Term
|
Definition
| Complete blood count, usually includes WBC, RBC, Hb, Hct, red cell indices (MCV, MCH, MCHC) and platelet count. other tests listed under the CBC include red cell distribution width (RDW), mean platelet volume (MPV) and a differential examination of the quality and quantity of various WBC reported wither in % or absolute terms. |
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Term
|
Definition
| reports % of the types of WBC present. neutrophils, lymphocytes, monocytes, eosinophils and basophils. |
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Term
|
Definition
| a measure of how long it takes blood to clot by evaluating clotting factors in the extrinsic pathway. Prothrombin, or factor II, is one of several clotting factors produced by the liver. adequate amounts of Vit K are needed to produce protrombin. PT measures the presence and activity of 5 different blood clotting factors (I, II, V, VII and X) |
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Term
|
Definition
| partial thromboplastin time; evaluates the factors found in teh intrinsic and common pathways. sues blood to which a chemical has been added to prevent clotting before the test begins. blood is drawn, centrifugated, Ca and activating substances are added to the plasma to start the intrinsic pathway |
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Term
|
Definition
| human blood is classified, or typed, according to the presence or absence of certain natigens on the surface of RBC. most important antigens are blood group antigens ABO and the Rh antigen. |
|
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Term
|
Definition
| weakness, fatigue, pallor, bruisability, lymphadenopathy, bleeding, purpura, lab results: neutrophilia, neutropenia, eosinophilia, eosinopenia, monocytosis, monocytopenia, basophil disorders. |
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|
Term
| Cellularity (Dr. Christman) |
|
Definition
| ratio of cells to fat spaces. ratio is age dependent with normal adult being 1:1. |
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Term
|
Definition
| ratio of granulocytes to erythroid precursors normal ratio of 3:! |
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|
Term
| Megakaryocytes (Dr. Christman) |
|
Definition
| largest cells in marrow with multiple nuclei, give rise to platelets by cytoplasmic budding. |
|
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Term
|
Definition
| erythrocytes, granulocytes, monocytes and platelets |
|
|
Term
| Normal Hematopoiesis locations (Dr. Christman) |
|
Definition
| bone marrow of vertebrae, ribs, sternum, skull and pelvis! |
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|
Term
| Anemia; physiologic definition (Dr. Christman) |
|
Definition
| reduction in oxygen carrying capacity of blood |
|
|
Term
| Anemia; Physiologic definition (Dr. Christman) |
|
Definition
| Reduction below normal limits of total ciculating red cell mass as measured by hemoglobin concentration or hematocrit (volume of packed red blood cells) |
|
|
Term
| Hemolytic Anemia classification (Dr. Christman) |
|
Definition
| increased rate of destruction; intrinsic abnormalities of RBC: RBC membrane disorders, RBC enzyme deficiencies, Hb synthesis abnormalities- deficient globin chain synthesis, structurally abnormal globin chains; Extrinsic abnormalities of red cells: antibody mediated destruction, mechanical trauma, hypersplenism |
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|
Term
| Anemia S&S (Dr. Christman) |
|
Definition
| pallor, weakness, dyspnea on exertion. If severe enough may also lead to myocardial and central nervous system hypoxia. |
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|
Term
| Most common nutritional deficiency in the world |
|
Definition
|
|
Term
| Fe deficient anemia etiology (Dr. Christman) |
|
Definition
| Dietary lack, impaired absorption, increased requirements, chronic blood loss. Iron deficiency in adult males and postmenopausal women in the Western world should be considered to be caused by GI blood loss until proven otherwise. |
|
|
Term
| Fe deficient anemia morphology (Dr. Christman) |
|
Definition
| hypochromic microcytic anemia represented in the peripheral blood smear by paler (hypochromic) and smaller (microcytic) than normal red cells. |
|
|
Term
| Fe deficient anemia laboratory diagnosis (Dr. Christman) |
|
Definition
| serum Fe- decreased, serum ferritin- decreased, total iron binding capacity- increased, transferrin saturation- decreased, mean cell volume- decreased, bone marrow iron- decreased or absent |
|
|
Term
| Megaloblasic anemia (Dr. Christman) |
|
Definition
| diverse group of disorders having in common impaired DNA synthesis with distinctive morphologic changes in the blood and bone marrow. Deficiencies or impaired utilization of vitamin B12 and/or folate, both coenzyme sin teh DNA synthesis pathwy, are the principal causes of megaloblastic anemia. because RNA synthesis proceeds unimpeded in the cytoplasm, asynchrony between nuclear DNA and cytoplasmic RNA maturation develops. |
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|
Term
| Megaloblastic Anemia morhology (Dr. Christman) |
|
Definition
| erythrocytes are larger than normal and oval shaped. Neutrophils are also larger and hypersegmented with five to six or more nuclear lobules. The bone marrow is hypercellular with large red cell precursors containing fine chromatin and enlarged granulocytes. |
|
|
Term
| Enlarged granulocytes (Dr. Christman) |
|
Definition
| Giant bands and metamyelocytes |
|
|
Term
| Megaloblast (Dr. Christman) |
|
Definition
| large red cell precursor containing fine chromatin |
|
|
Term
| B12 deficiency etiology (Dr. Christman) |
|
Definition
| inadequate diet; impaired absorption- intrinsic factor deficiency, pernicious anemia, gastrectomy; malabsoprtion states- sprue, ileal resection, inflammation; competitive uptake- parasitic infection, intestinal bacterial overgrowth; increased requirement- pregnancy |
|
|
Term
Absorption of B12 requires...
(Dr. Christman) |
|
Definition
| intrinsic factor (IF) which is secreted by parietal cells of the gastric mucosa. |
|
|
Term
B12 is absorbed...
(Dr. Christman) |
|
Definition
| following ingestion of animal products, B12 is liberated via combination of gastric and pancreatic enzymes and transported to the duodenum. Once free B12 reaches the duodenum, it attaches to intrinsic factor forming the B12-IF complex which is then absorbed in the terminal ileum. Following absoprtion, B12 complexes with transcobalamin II which transports it to the cells of the body. |
|
|
Term
| biochemical functions of B12 (Dr. Christman) |
|
Definition
| DNA synthesis, Maintenance of myelin surrounding neurons. In conjunction with a reversible megalobastic anemia, B12 deficiency results in neurologic complications with eventually become irreversible. |
|
|
Term
| Pernicious Anemia (Dr. Christman) |
|
Definition
| felt to be caused by immunologically mediated autoimmune destruction of gastric mucosa, the result of which is a marked loss of intrinsic factor producing parietal cells. (B12 absorption) |
|
|
Term
| Autoantibodies present in pernicious anemia (Dr. Christman) |
|
Definition
| IgG anti-instrincic factor detecred in 75% of patients, anti-parietal cell antibody detected in 85-90% of patients. |
|
|
Term
| Morphology of pernicious anemia (Dr. Christman) |
|
Definition
| megaloblastic anemia, gatric atrophy with intestinal metaplasia, central nervous system lesions consisting of myelin degeneration of dorsal and lateral columns of the spinal cord (subacute combined degeneration) |
|
|
Term
| diagnostic features of pernicious anemia (Dr. Christman) |
|
Definition
| megaloblastic anemia (macro-ovalocytes with MCV>100), hypersegmented neutrophils, neurologic manifestations-paresthesias, sensory ataxias, presence of autoantibodies, elevated urinary methylmalonic acid, low serum B12, schilling test. |
|
|
Term
| Schilling test (Dr. Christman) |
|
Definition
| patients are given an injection of B12 to saturate binding sites within the body. A radiolabelled dose of B12 is then given orally and a 24 hours urine specimen is collected. SInce binding sites have already been saturated by parenteral injection, all B12 that is properly absorbed is excreted and detected in the urine. In part II, intrinsic factor is given with oral B12. |
|
|
Term
| Schilling test in PA (Dr. Christman) |
|
Definition
| Radiolabelled B 12 is not present in the urine since the oral dose is not absorbed (part I). In part II the radiolabelled B12 is detected in the urine because the exogenous intrinsic factor given forms the B12-IF complex required for absorption in the terminal ileum. |
|
|
Term
| Folate deficiency (Dr. Christman) |
|
Definition
| results in megaloblastic anemia identical to B12 deficiency. However, the neurologic manifestation encountered in B12 deficiency does not occur. |
|
|
Term
| Folate deficiency etiology (Dr. Christman) |
|
Definition
| decreased intake- inadequate diets of chronic alcoholics and indigent; increased requirement- pregnancy and infancy; impaired utilization- folate antagonists (chemotherapeutic agents) |
|
|
Term
| Diagnositc features of Folate deficiency (Dr. Christman) |
|
Definition
| megaloblastic anemia (macro-ovalocytes with MCV>100); hypersegmented neutrophils; low serum and RBC folate levels; prompt hemtologic response following administration of folate; elevated urinary levels of formiminoglutamic acid. |
|
|
Term
| Anemia of chronic disease AOCD (Dr. Christman) |
|
Definition
| refers to impaired red cell production associated with chronic diseases and represents the most common cause of anemia among hospitalized patients in the US. AOCD is associated wth defective iron utilization and may therefore mimic iron deficiency. |
|
|
Term
| Diseases associated with AOCD (Dr. Christman) |
|
Definition
| chronic infetions- osteomyelitis, lung abcesses, endocarditis; chronic immune disorders- rheumatoid arthritis, Crohn's diseases; neoplasms- hodgkin's disease, carcinoma. |
|
|
Term
| Etiology of AOCD (Dr. Christman) |
|
Definition
| felt to be the result of elevated levels of various cytokines (IL-1, TNF) seen in inflammatory conditions. There cytokines somehow divert iron into the marrow storage pool instead of erythrocyte precursors which require it for hemoglobin synthesis. End result is low serum iron with reduced iron binding capacity coupled with abundant storage of iron in the bone marrow. |
|
|
Term
| Morphology of AOCD (Dr. Christman) |
|
Definition
| normochormic/normocytic anemia or hypochromic/microcytic anemia. |
|
|
Term
| Lab diagnosis of AOCD (Dr. Christman) |
|
Definition
| low serum iron, decresed or normal total iron binding capacity (TIBC), elevated ferritin levels, increased iron in marrow macrophages. |
|
|
Term
| Treatment of AOCD (Dr. Christman) |
|
Definition
| AOCD is generally mild with treatment of the underlying condition correcting the anemia. |
|
|
Term
| Hemolytic anemias (Dr. Christman) |
|
Definition
| shortening of RBC life span, accumulation of products of hemoglobin catabolism (bilirubin), compensatory increase in erythropoiesis within bone marrow. |
|
|
Term
| Intravascular hemolysis (Dr. Christman) |
|
Definition
| Normal RBCs are damaged by mechanical trauma (prosthetic heart valves), complement fixation (mismatched blood transfusion) or exogenous toxins (malaria, sepsis) and subsequently destroyed within the vascular system. |
|
|
Term
| Manifestations of intravascular hemolysis (Dr. Christman) |
|
Definition
| hemoglobinemia, hemoglobinuria, jaundice (unconjugated hyperbilirubinemia), decreased haptoglobin |
|
|
Term
| Haptoglobin (Dr. Christman) |
|
Definition
| a plasma protein which binds released free hemoglobin following intravascular hemolysis. Haptoglobin-hemoglobin complex is then cleared by the reticuloendothelial system resulting in decreased serum haptoglobin in intravascular hemolysis hemolytic anemia. |
|
|
Term
| Extravascular hemolysis (Dr. Christman) |
|
Definition
| RBC are rendered foreign or become less deformable with destruction/lysis occuring within the spleen. Most hemolytic anemias fall within this category. Because hemolysis is extravascular; hemoglobinemia, hemoglinuria and depleted haptoglobin are not features of extravascular hemolysis. |
|
|
Term
|
Definition
| Hyperbilirubinemia is characteristic of both intravascular and extravascular hemolysis and patients with hemolytic anemias are therefore predisposed to the development of bilirubin containing gallstones. |
|
|
Term
| Hereditary Shperocytosis (Dr. Christman) |
|
Definition
| autosomal genetic condition characterized by intrinsic defect in red cell membrane that renders erythrocytes spheroidal as opposed to normal biconcave disc shape. With a spheroidal shape, RBCs are less deformable and vulnerable tot splenic destruction. |
|
|
Term
| Pathogenesis of hereditary spherocytosis (Dr. Christman) |
|
Definition
| the spheroidal shape results from deficiencies of red cell membrane proteins, the most common of which is ankyrin. With deficient ankyrin, reduced membrane stability and spontaneous loss of red cell membrane fragments occurs. Spheroidal cells can no longer navigate th splenic cords and become trapped and phagocytized by splenic macrophages. |
|
|
Term
| Morphology of spherocytosis (Dr. Christman) |
|
Definition
| spheroidal RBC in peripheral blood smear, splenomagaly, pigmented gallstones |
|
|
Term
| Hemolytic crisis (Dr. Christman) |
|
Definition
| massive hemolysis with fever, abdominal pain, worsening jaundice and possibly shock. Seen in spherocytosis. |
|
|
Term
| Aplastic crisis (Dr. Christman) |
|
Definition
| triggered by "parvovirus" infection of red cell precursors in marrow and characterized by suppression of red cell production. Seen in spherocytosis. |
|
|
Term
| Hemolytic Anemia Definition (Dr. Inhorn) |
|
Definition
| premature destruction of RBC. destruction can occur in two locations, extrinsic- reticuloendothelial system, intrinsic- in the blood vessels |
|
|
Term
| Hallmark of hemolytic anemias (Dr. Inhorn) |
|
Definition
| elevated reticulocyte count in the setting of anemia. This is a compensatory response to premature loss of eythrocytes, the only other condition that causes anemia with reticulocytosis is acute bleeding. |
|
|
Term
| Anemia of increased destruction indicates (Dr. Inhorn) |
|
Definition
| normochromic, shortened RBC survival, reticulocytosis- response to increased RBC destrution, increased indirect bilirubin, increased LDH, decreased haptoglobin. |
|
|
Term
| Differential diagnosis for Hemolytic Anemia (Dr. Inhorn) |
|
Definition
| hemoglobinopathies, disorders of the erythrocyte membrane, erythrocyte enzymopathies, causes extrinsic to the erythrocyte, immune hemolysis. |
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Term
| Hemoglobin structure (Dr. Inhorn) |
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Definition
| The major hemoglobin in adults is hemoglobin A- tetramer consisting of one pair of alpha chains and one pair of beta chains. In normal subjects globin chain synthesis is very tightly controlled- production of alpha to non-alpha chains is 1.00 +/- 0.05. There are two copies of the alpha chain gene on chromosome 16, and one beta globin gene on chromosome 11 |
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Term
| Thalassemia definition (Dr. Inhorn) |
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Definition
| referes to a spectrum of diseases characterized by reduced or absent production of one or more otherwise normal globin chains. |
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Term
| Hemoglobinopathy definition (Dr. Inhorn) |
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Definition
| refer to production of an abnormal globin chain |
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Term
| Alpha thalassemia (Dr. Inhorn) |
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Definition
| alpha thalassemia is due to impaired produciton of alpha globin chains, leads to relative excess of gamma globin chains in the fetus and newborn and beta globin chains in children and aduts. The excess beta globin chains are capable of forming soluble tetramers (beta-4 or HbH) HbH is unstable and precipitates within the call, leading to clinical manifestations. |
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Term
| Homozygous alpha (Dr. Inhorn) |
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Definition
| (O) incompatible with extrauterine life, leading to hydrops fetalis and/or death shortly after delivery. |
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Term
| Beta thalassemia definition (Dr. Inhorn) |
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Definition
| due to impaired production of beta globin chains, which leads to excess alpha globin chains. Alpha globin is not able to form soluble tetramers and precipitates within the cell. |
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Term
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Definition
| (aa/a-) clinically normal |
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Term
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Definition
| (a-/a- or aa/--). Clinically normal but may have mild anemia and decreased MCV |
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Term
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Definition
| (a-/--) moderate to severe lifelong hemolytic anemi, splenomegaly, bone changes and ineffective erythropoiesis. |
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Term
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Definition
| also called beta thalassemia trait. heterozygous. clinically asymptomatic, mildly anemic. hypochromia and microcytosis (MCV<75) anemia (Hct>30) RBC # higher. target cells common. Hb A2 typically elevated. |
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Term
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Definition
| no effective production (homozygous beta (O)) or severely limited productiono f beta globin. also called cooley's anemia. results in severe hemolytic anemia, hepatosplenomegaly, skeletal deformities, infections, iron overload. |
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Term
| beta thalassemia intermedia |
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Definition
| some beta globin production, resulting in diseases of intermediate severity |
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Term
| thalassemia nomenclature (Dr. Inhorn) |
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Definition
(+) indicates diminished, but some production of globin chain by gene
(O) indicates no production of globin chain by gene. |
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Term
| Classifications and terminology of beta thalassemia (Dr. Inhorn) |
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Definition
| normal (B/B); minor (B/B0) (B/B+); intermedia (B0/B+); Major (B0/B0) (B+/B+) |
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Term
| symptoms of beta thalassemia (Dr. Inhorn) |
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Definition
| pallor, growth retardation, hepatosplenomegaly and jaundice from hemolyic anemia. |
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Term
| Lab features of Beta thalassemia (Dr. Inhorn) |
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Definition
| profoudn microcytic anemia and bizarre red cell morphology- microcytes, tear drop and target cells, clumped inclusion bodies from alpha globin precipitation. low reticulocyte count (ineffective erythropoiesis), splenomegaly may cause low WBC and platelet counts, serum iron elevated from high rate of RBC turnover. high levels of indirect bilirubin and LDH with low levels of haptoglobin are typical of hemolytic anemia. |
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Term
| Clinical features of beta thalassemia (Dr. Inhorn) |
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Definition
| chipmunk facies, delayed skeletal maturation, sexual development delay, expansion of marrow widens the marrow spaces and attenuates the cortex causing osteoporosis, hepatomegly occurs early due to increased red cell destruction and extramedullary erythropoiesis. accelerated iron turnover results in chronic iron overload. bilirubin gallstone disease. gouty arthritis, cardiac malfunction, CHF, fatal arrythmias. |
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Term
| Yersinia infection (Dr. Inhorn) |
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Definition
| yersinia enterocolitica is a significant cause of morbidity in patients with thalassemia and other iron overload syndromes (chronic liver disease, hereditary hemochromatosis). Y.entero is siderophilic (iron is essential for its growth). Iron chelation with desferrioxamine makes iron more bioavailable to Y entero. direct early anti-yersinia therapy in pts with appendicitis-like syndrome. |
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Term
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Definition
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Term
| Alpha thalassemia clinical features (Dr. Inhorn) |
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Definition
| alpha thalassemia minima essentially asymptomatic. alpha thalassmia minor resembles minor beta thalassemia trait. hypochromia, microcytosis and target cells. elevation of Hb A2 does not occur. |
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Term
| Hemoglobin H disease (Dr. Inhorn) |
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Definition
| more severe than alpha thalassemia trait, dramatically left-shifted oxygen disassociation curve, virtually useless for oxygen delivery, insoluble, chronic hemolytic anemia results. |
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Term
| Hb H disease clinical features (Dr. Inhorn) |
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Definition
| chronic hemolytic anemia, including HSM, elevated bili and LDH, decreased haptoglobin and biliary disease. fewer skeletal complications than beta thalassemia. disease resembles beta thalassaemia intermedia in severity. iron overload common, splenectomy or institution of transfusion support during 2nd or 3rd decade of life often necessary. |
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Term
| Alpha thalassemia treatment (Dr. Inhorn) |
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Definition
| alpha thalassemia minima and minor require no treatment. Hb H disease often requires transfusional suport and iron chelation. watch carefully during times of oxidative stress, such as infection. |
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Term
| Beta thalassemia minor treatment (Dr. Inhorn) |
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Definition
| no specific therapy. avoid inappropriate iron therapy. monitor ferritin levels, consider chelation if serum ferritin exceeds 1000ng/mL. |
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Term
| Beta thalassemia major treatment (Dr. Inhorn) |
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Definition
| chronic hypertransfusion, splenectomy and iron chelation. transfuse aggresively to maintain hemoglobin of 9-10. decrease HSM, skeletal problems, cardiac dilatation. splenectomy used with increase in red cell transfusion requirement. |
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Term
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Definition
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Term
| Sickle Cell Disease definition (Dr. Inhorn) |
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Definition
| most common hemoglobinopathy seen in clinical practice. Hb S results from substitution of Val for Glutamic acid at teh 6th AA of the beta globin chain. Deoxy HgS polymerizes and leads to aletered red cell membrane structure and function. Vaso-occlusive phenomena and hemolysis are clinical hallmarks. |
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Term
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Definition
| hemoglobin electrophoresis is definitive test. five minute solubility test, Sickledex, used to detect the presence of HbS in the emergency setting- doe snot differentiate sickle syndromes from benign carrier state. |
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Term
| SCD lab findings (Dr. Inhorn) |
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Definition
| chronic hemolysis causes mild to moderate anemia (Hct 20-30). Retic count 3-15% causes elevated MCV. unconjugated hyperbili, elevated LDH, low haptoglobin. sickled cells, polychromasia, Howell-Jolly bodies (hyposlenia 2ndary to repeated splenic infarctions) HbF slightly elevated. |
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Term
| Anemia in SCD (Dr. Inhorn) |
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Definition
| chronic anemia, well compensated hemolytic anemia with appropriate reticulocytes. Inappropriately low EPO level in adults with renal disease. Folate and/or iron deficiency from increased folate utilization or urinary iron losses (check ferritin level). Acute severe anemia can be seen: splenic sequestration crisis, aplastic crisis (Parvovirus B19), hyperhemolytic crisis (rare). |
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Term
| Clinical features of SCD (Dr. Inhorn) |
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Definition
| acute pain episodes, more pain seen in pts with high Hb (>8.5) and low Hb F. pain precipitated by cold, dehydration, infection, menses, EtOH. typical crisis 2-7 days. Multiorgan failure is potentially fatal syndrome, growth failure and delayed puberty common. infection, splenic infarction (age 4). Osteomyelitis- Salmonella not Staph. neuro complications (TIA, CVA) silent infarcts, retinopathy common. hand-foot syndrome (dactylitis). acascular necrosis. |
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Term
| acute chest syndrome (Dr. Inhorn) |
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Definition
| 30-50% SCD pts, clinical sxs- chest pin, new infiltrate on CXR and fever, frequent cause of death in adults, etiology- vaso-occlusion (R/O infarction, embolism, and pneumonia). TxtL supportive care, antibiotics, O2, analgesic, volume repletion, exchange transfusion. chronic problems include restrictive or obstructive lung ds, hypoxemia, pulmon HTN. |
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Term
| renal manifestations of SCD (Dr. Inhorn) |
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Definition
| painless hematuria due to papillary infarcts, renal infarction, papillary necrosis and renal colic (papillary necrosis can be seen in sickle trait), nephrogenic DI, focal glomerulosclerosis can lead to end-stage renal ds, urinary concentration ability challenge (isosthenuria). priapism occurs in 6-42% of males, can cause impotence. |
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Term
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Definition
| Hemolysis, Hand foot syndrome, bone marrow hyperplasia/infarction, stroke, skin ulcers, pain episodes, priapism, anemia, aplstic crisis, avascular necrosis, infections, nocturia, urinary frequency from hyposthenuria, cholelithiasis, cardiomegaly, CHF, chest syndrome, retinopathy, renal failure, renal concentrating defects, infarction, sequestration crisis involving spleen or liver, increased fetal loss during pregnany, sepsis. |
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Term
| management of SCD (Dr. Inhorn) |
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Definition
| largely supportive, IV fluids, oxygen, analgesics, incentive spirometry, folic acid, antibiotics as indicated. exchange transfusion for severe complications (multiorgan failure, priapism, acute chest syndrome, stroke) |
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Term
| Kleihauer- Betke Smear (Dr. Allegretta) |
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Definition
| test for HbF present in blood. Acid removes adult Hb, but not HbF (HbF is abnormal after two weeks of age) then stains HbF pink. |
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Term
| Fetal Marrow development- in utero (Dr. Allegretta) |
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Definition
| normoblastic= 90% @10th week. liver is primary site form 3rd-6th month. marrow is primary site from 6th month. myeloid development starts in ~4th month. blood is rich in progenitors- cord blood transplants |
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Term
| Fanconi Anemia (Dr. Allegretta) |
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Definition
| o people with FA may also have physical finding, which are highly variable and may include short stature, upper limb differences, kidney, cardiac and GI problems, brown pigmented sports on the skin, hearing loss and developmental delay |
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Term
| Hematologic findings in megaloblastic condition (Dr. Allegretta) |
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Definition
| increased MCV, multisegmetned neutrophils, HOwell-Jolly bodies- black dots in cytoplasm= messed up DNA |
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Term
| Fetal hydrops ultrasound findings (Dr. ALlegretta) |
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Definition
| severe anemia- parvovirus B19; pleural effusion, ascites, scalp edema |
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Term
| Cardiac compensation to hypoxia (Dr. Allegretta) |
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Definition
| increased HR may lead to high output heart failure. Cardiac output=SV*HR; hypoxia requires increased cardiac output, HR increased first, stroke volume increased by Starling's law. |
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Term
| Leukoerythroblastic blood smear (Dr. Allegretta) |
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Definition
| Peripheral blood smear. Large WBC, nucleated red cells (marrow cells in circulation), tear drop red cells. malignancy until proven otherwise after first week of life. |
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Term
| Newborn "Unusual" definition of normal (Dr. Allegretta) |
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Definition
WBC may be high (30K) and go up next day (34K) in newborn. Leukoerythroblastic smear
Dx= normal. |
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Term
| Newborn Iron acquisition (Dr. Allegretta) |
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Definition
| fetus rapidly accumulates Hgb and Fe. Newborn will have normal Hgb and ferritin even id mother has mild-moderate iron deficiency- may cause prematurity, LBW. Fe content at birth= ~75mg/kg. varies with cord clamping technique. Fe deficiency rare before 4 months of age. Neither human nor cow's milk has iron. Fe absorption better with human milk (lactoferrin) |
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Term
| Postnatal Erythropoiesis (Dr. Allegretta) |
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Definition
| RBC decreases 10fold during 1st week. mechanism unknown, EPO level=0. increases from wk2-3months. consequence- physiologic anemia, marked iron demand increase from 4mos-12mos due to body mass growth. |
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Term
| RBC related conditions of the infant (Dr. Allegretta) |
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Definition
| fetal blood loss (Rare), jaundice (very common), newborn immune hemolysis (occasional), congenital RBC aplasia (rare) |
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Term
| Jaundice in the newborn (Dr. Allegretta) |
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Definition
| fundamentals of physiology- bilirubin produced by RBC breakdown, newborn conjugates poorly, lab: T/D. direct bili= conjugated; indirect bili= unconjugated. Common: increased indirect bilirubin (1/0.2)- physiologic; breast milk; RBC destruction. Uncommon: increased direct bilirubin- cholestasis (abnormal ducts; sepsis;mass) |
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Term
| Biliary atresia (Dr. Allegretta) |
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Definition
| rare condition in newborns; common bile duct between the liver and the small intestine is blocked or absent; condition leads to liver failure but not kernicterus. liver is still able to conjugate bilirubin, and conjugated bilirubin is unable to cross the blood-brain barrier. The cause of the condition is unknown. The only effective treatments: surgeries, or liver transplantation. |
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Term
| Bilirubin toxicity (Dr. Allegretta) |
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Definition
| Kernicterus- deafness, retardation, caused by staining of basal ganglia. risk level: > 20 if hemolysis. |
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Term
| jaundice evaluation (Dr. Allegretta) |
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Definition
| examination for hepatomegaly, labs: bili T/D, ? hemolysis, SGOT, SGPT, LDH, Retic, CO-Hgb, maternal ABO, Liver function studies. |
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Term
| SGOT, SGPT (Dr. Allegretta) |
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Definition
| hepatic enzymes. Levels change in jaundice- specifics not needed for examination |
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Term
| Management of Jaundice (Dr. Allegretta) |
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Definition
| hydration, phototherapy (isomerize unconjugated bilirubin, degrades bilirubin to biliverdin) exchange transfusion. |
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Term
| Newborn isoimmune hemolysis- Rh (Dr. Allegretta) |
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Definition
| anti-D (Rh); setup= mother Rh-, IgG Antibody +, infant is Rh +. Mechanism= maternal anti-D IgG crosses placenta, binds fetal RBC, fetal macrophages destroy RBC. Consequences= jaundice, anemia, intrauterine CHF. |
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Term
| Prevention and treatment for isoimmune hemolysis (Rh) (Dr. Allegretta) |
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Definition
| Rhoga (IM anti-D Antibody) at 28 weeks and at delivery. treatment- follow anti-D levels, amniocentesis (bilirubin) fetal ultrasound- scalp edema--> transfusion, infant- exchange transfusion. |
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Term
| Isoimmune hemolysis (ABO) (Dr. Allegretta) |
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Definition
| ABO incompatibility. setup= mother type O; mechanism- antibody is usually anti-A isohemaglutinnin. Infant- jaundice before anemia, spherocytes, RBC membrane destruction. |
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Term
| Congenital hypoplastic anemia (Dr. Allegretta) |
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Definition
| Blackfan-Diamond anemia, fault in one of the early steps of RBC production, 25% have a gene called RPS19. short for small ribosomal protein 19. |
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Term
| Symptoms of congenital hypoplastic anemia (Dr. Allegretta) |
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Definition
| fatigue, pallor, open mouth facies, protruding scapulae, web neck, cardiac abnormalities. |
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Term
| Diagnosis and treatment of Congential hypoplastic anemia (Dr. Allegretta) |
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Definition
| infantile normochromic, macrocytic anemia, reticulocytoplenia, normocellular marrow with deficiency of RBC precursors. Txt: transfusions, steroids, marrow transplant. |
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Term
| Evaluating an anemia (Dr. Allegretta) |
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Definition
| increased destruction- immune, not immune; decreased production- marow disease, marrow invasion; blood loss- GI tract |
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Term
| Iron deficiency anemia presentations (Dr. Allegretta) |
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Definition
| physical performance and growth- restless leg syndrome, weakness, dyspnea, sexual dysfunctions, HA; intellectual performance and growth- attention deficient disorder, cognitive or behavioral dysfunction, fatigue, depression; GI- pica, anorexia, HA, burning tongue; Endocrine- increased menstrual blood; Immune- increased severity of infections; Skin- pruritis, paresthesias, pallor. |
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Term
| Stages of iron deficiency (Dr. Allegretta) |
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Definition
| decreased stores (decreased ferritin), decreased transferrin saturation, morphological changes- anisocytosis, normochromic normocytic anemia, decreased Hgb, decreased MCV, decreased MCHC; thrombocytosis, bone marrow depletion. |
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Term
| Common cause of anemia is children (Dr. Allegretta) |
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Definition
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Term
| Nutritional causes of anemia in teens (Dr. Allegretta) |
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Definition
Women= chocolate
Men= burgers
Burgers > iron. Chocolate < iron. |
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Term
| Serum Ferritin (Dr. Allegretta) |
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Definition
| generally correlates with iron stores. normal ferritin at 6mos-15 years lower than other ages. Taking Fe increases ferritin. Normal ferritin= newborn (25-200ng/ml), 1st month (200-600), 2-5months (50-200), >5months (7-140), adult male (20-250), adult female (10-120) |
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Term
| Lead poisoning (Dr. Allegretta) |
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Definition
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