Unit 2 Flashcards

Question

How do mature erythrocytes metabolize glucose?

Answer 1

Anaerobic glycolysis `

Answer 2

- increased concentration of erythrocytes in the circulating blood that is above normal for gender and age

Answer 3

- disorder of erythropoietin - also called absolute polycythemia - reflect an increase in erythropoietin production and should not be confused with polycythemia Vera

Answer 4

- presence of high oxygen affinity hemoglobin - chronic lung disease - smoking - dwelling in high altitudes

Answer 5

- can result from conditions that are not related to increased erythropoietin production. These conditions include the relative polycythemia

Answer 6

- rarely has to do with the cells, but rather the proportion of cells to plasma volume - when plasma volume is lowered, for example, it will appear as through the Hct is higher than expected, but it is not

Answer 7

Refers to all of the stages of erythrocyte development

Answer 8

- Glycoprotein hormone (can cross placenta) - androgen hormone - thyroid hormone

Answer 9

- a decrease in the oxygen content within the tissues - produces dramatic increase in EPO production

Answer 10

1. The number of hemoglobin-containing erythrocytes increases 2. The oxygen-carrying capacity of the blood increases 3. Th normal level of oxygen in the tissues can be restored

Answer 11

- the committed erythroid cell, CFU-E, promoting their proliferation and differentiation into erythroblasts - also stimulates the differentiation of a more primitive erythroid differentiation of a more primitive erythroid progenitor, BFU-E, with bursting-promoting activity

Answer 12

Cell apoptosis

Answer 13

- erythropoietin - iron - vitamins - hormones

Answer 14

- neoplasms - renal disorders that produce local hypoxia within the kidney - second polycythemia

Answer 15

- seen in certain anemias, such as vitamin B12 or folate deficiencies - most noticeable characteristics of this type of defect is the nuclear maturation lags behind cytoplasmic maturation - Because of an impaired ability of the cells to synthesize DNA, both the interphase and the phases of mitotic divisions are prolonged

Answer 16

Because the nuclear development of the cells is much younger looking than the actual development age, which is expressed by the cytoplasmic development

Answer 17

- has limited ability to metabolized fatty acids and amino acids and lacks mitochondria for oxidative metabolism

Answer 18

- exclusively produced by anaerobic glycolysis, through the Embden-Meyerhof-Parma’s pathway, mainly, but also get assistance through: —> hexose monophosphate shunt —> methemoglobin reductase pathway —> luebering-Rapoport pathway

Answer 19

- may be subdivided into the following: —> major anaerobic embden-Meyerhof glycolytic pathway that generates ATP and maintains the function of the hemoglobin —>three supplementary pathways 1. The methemoglobin reductase pathway 2. The Rapoport-Luebering pathway 3. The phosphogluconate pathway

Answer 20

- in maturing reticulocyte, membrane vesiculation leads to loss of surface area - posses a significant amount of tubulin and actin in the membrane that mature RBC and therefore gets lost

Answer 21

- increase in shear resistance - loss of surface area because of membrane lipid loss - acquisition of a bioconcave shape

Answer 22

- shape of erythrocyte constantly changes as it moves through the circulation - composed of a protein lattice-lipid bilayer to which the membrane skeleton is attached by trans bilayer (peripheral proteins) - deformable and tolerant against mechanical stress and various pH and salt concentrations in vivo and in vitro - cell shape changes reversibly depending on ATP level in the cell and intracellular calcium ion concentration

Answer 23

- composed for peripheral proteins that control cell shape, attachment to other cells and maintain organization of specialized membrane domains - major components are alpha- and beta- spectrin, ankyrin, band 3, band 4.2, and the glycophorins - together they form a complex meshwork tethered to the RBC membrane

Answer 24

Water transporter

Answer 25

- anion transporter - support system for surface antigens of ABH blood groups antigens

Answer 26

Calcium transporter

Answer 27

- glucose transport - supports ABH blood group antigens

Answer 28

- transport negatively charged sialic acid - supports MN blood group antigens

Answer 29

- transport negatively charged sialic acid - supports Ss blood groups antigens

Answer 30

- transport negatively charged sialic acid - supports Gerbich blood group system antigens

Answer 31

- integrin adhesion

Answer 32

- Zn binding endopeptidase - supports Kell blood group antigens

Answer 33

- urea transporter

Answer 34

Supports D and CcEe blood group antigens

Answer 35

- Supports DCcEe antigen expression - gas’ transporter (probably CO2)

Answer 36

- maintains cellular energy by generating ATP

Answer 37

- prevents denaturation of globin of the hemoglobin molecule by oxidation

Answer 38

- keeps hemoglobin in the reduced state, which prevents oxidation of hemoglobin (heme iron)

Answer 39

Regulates oxygen affinity of hemoglobin

Answer 40

1. Water transporter, aquaporin 1 2. glucose transporters (GLOTI1 and GLUT3), sodium/hydrogen exchanger 1 3. Na-K-ATPase

Answer 41

1. Yolk sac 2. Liver and spleen 3. Red bone marrow

Answer 42

Liver and spleen

Answer 43

- polychromatophilia

Answer 44

When the plasma volume is decreased

Answer 45

- decreases the oxygen affinity of the hemoglobin molecule

Answer 46

The molecule expels 2,3 DPG

Answer 47

- no mitochondria for oxidative metabolism

Answer 48

- high in potassium ions - glucose and enzymes necessary for glycolysis

Answer 49

- maintain membrane lipids - power the cation pump needed for sodium-potassium concentration pump and calcium flux - preserve the shape and flexibility of the cellular membrane

Answer 50

- lactate - 2 ATPS

Answer 51

Pyruvate kinase

Answer 52

- insufficient amounts of reduced glutathione - denaturation of globin - precipitation of Heinz bodies

Answer 53

Reduced amounts of glutathione

Answer 54

Glycolysis is reduced

Answer 55

- enzyme activity, particularly glycolysis, decreases

Answer 56

Macrophages of the spleen

Answer 57

- age-related changes can be monitored using plasma membrane calcium (PMCA) and glycated hemoglobin (Hgb A1C) —> PMCA strength declines as the RBC ages —> Hgb A1C increases as the RBC ages - these cause densification of the RBC membrane that contributes to the membrane instability seen in senescent RBCs

Answer 58

- in addition to hemoglobin, the enzymes synthesized during early cell development have to be sufficient to provide the energy needed for these processes —> main thing hemoglobin iron in an active ferrous (Fe2+) state —> driving the cation pump needed to maintain intracellular sodium ion (Na+) and potassium ion (K+) concentrations despite the presence of a concentration gradient —> maintaining the sulfrahydryl groups of globins, enzymes, and membranes in an active reduced state —> preserving the integrity of the membrane

Answer 59

- the life span of the erythrocyte is reduced and hemolysis results. Defects in metabolism can include the following —> failure to provide sufficient reduced glutathione,which protects other elements in the cell from oxidation —> insufficient energy-providing co-enzymes such as NADH, NADPH, and ATP

Answer 60

- involves the Embden-Meyerhof Parnas glycolytic pathway, are deficiencies of: —> G6PD —> pyruvate Kinase (PK)

Answer 61

- responsible for converting glucose-6 phosphate (G6P) to 6-phosphogluconate (6PG)

Answer 62

- converting pyruvate (pyruvic acid) to lactic acid

Answer 63

- generates 2 ATP from anaerobic glycolysis

Answer 64

- couples oxidative catabolism of glucose with NADP reduction, which is required for glutathione reduction - failure to reduce glutathione causes denaturation of globin and the formation of Heinz bodies

Answer 65

- allows for optimal oxygen transport in hypoxic conditions and acid-base disturbances though the accumulation of 2,3-DPG

Answer 66

- normal adult hemoglobin A is inherited in simple Mendelian fashion - four polypeptide chains (574 amino acids) —> two alpha and two beta chains —> each has an attached heme group - genotype for normal hemoglobin is A/A - there are approximately 350 variants types

Answer 67

- the oxygen affinity of the hemoglobin molecule is associated with the spatial rearrangement of the molecule and is regulated by the concentration of phosphates, particularly 2,3-DPG in the erythrocyte - 2,3-DPG combines with the beta chains of deoxyhemoglobin and diminishes the molecules affinity for oxygen

Answer 68

- 2,3-DPG combines with beta chains of deoxyhemoglobin and diminishes the molecules affinity for oxygen - heme groups unload oxygen in tissues and beta chains are pulled apart and 2,3-DPG form salt bridges - results in lower affinity of oxygen - oxygen uptake in lungs causes salt bridges to be broken and 2,3-DPG to be expelled - in cases of tissue hypoxia, oxygen moves from hemoglobin to tissues and amount of deoxyhemoglobin increases in RBC - produces binding of 2,3-DPG which lowers hemoglobin affinity of oxygen

Answer 69

- depletion of free 2,3-DPG leads t increased production of more 2,3-DPG and a persistently lowered affinity of the hemoglobin molecule for oxygen

Answer 70

- the ease with which hemoglobin can be loaded with oxygen in the lungs and unloaded in tissue

Answer 71

The relationship between oxygen content (% saturation) and partial pressure of oxygen (PO2)

Answer 72

- the partial pressure of oxygen required to produce half saturation of hemoglobin when the deoxyhemoglobin concentration equals the oxyhemoglobin concentration at a constant pH and temperature

Answer 73

- 7.4 - 37.5 C

Answer 74

- an increase in oxygen affinity is demonstrated by a shift to the left

Answer 75

A decrease in oxygen affinity is represented by a shift to the right, by a decrease in pH (Bohr effect), increase in temperature or hypoxia conditions

Answer 76

- indirectly by erythrocytes - directly by erythrocyte - in plasma

Answer 77

- predominant mechanism - approximately 3/4 of the activity for removing carbon dioxide, carbon dioxide diffuses into the erythrocytes, is catalyzed by the enzyme carbonic anhydrase, and is transformed into carbonic acid H2O + CO2 —> H2CO3 - the hydrogen ion of carbonic acid is accepted by the alkaline deoxyhemoglobin, and the bicarbonate ion diffuses back into the plasma H2CO3 —> H+ + HCO3-

Answer 78

- free bicarbonate diffuses out of RBC into plasma - plasma chloride diffuses into cell - in the lungs, bicarbonate is converted back into carbon dioxide and water and eliminate from lungs through respiration

Answer 79

- directly bound with deoxyhemoglobin forming carbamino hemoglobin

Answer 80

- carried in solution in the plasma to the lungs

Answer 81

- amino acid substitution (hemoglobinopathies) - diminished production of the polypeptide chains (thalassemias)

Answer 82

- hemoglobin is synthesized during most of the erythrocytic maturation process - 65% of cytoplasmic hemoglobin is synthesized before the nucleus is extruded - 35% is synthesized in the early reticulocyte

Answer 83

- mainly in the red bone marrow and liver - heme produced in the erythroid precursors is chemically identical to that in the cytochromes and myoglobin

Answer 84

- iron is delivered by transferrin to the membrane of immature cell - iron in the ferric form (Fe3+) affixes to cell membrane and transferrin is released - iron enters cell and proceeds to mitochondrion - excess iron accumulates as ferritin aggregates in the cytoplasm of immature erythrocyte

Answer 85

- the ratio between the plasma iron level and the iron required by the cell

Answer 86

- is a function of the rate at which the DNA code is transcribed

Answer 87

Chromosome 16 governs alpha chain production in adults and zeta chain production in the fetus - each cell has two chromosome 16 ( a total of 4 alpha chains in each cell) - mechanism of this coordination is unknown

Answer 88

Chromosome 11 governs the beta globin chains, which in order of sequence is epsilon, gamma, delta, and beta - two copies of gamma gene on each chromosome 11

Answer 89

Pairs two alpha globin chains and two beta globin chains together

Answer 90

- 141 amino acids in each alpha chain - 146 amino acids in each beta chain

Answer 91

Salt bridges are broken, and the hemoglobin molecule is describe as being relaxed (R) structure or state

Answer 92

- tetramer is stabilized by intersubunit salt bridges and is described as the tense (T) structure or state

Answer 93

T configuration is a low-oxygen affinity shape compared to the R configuration that is a high-oxygen conformation

Answer 94

- oxygenation of one site on a hemoglobin molecule enhances affinity for oxygen at a different but chemically identical site

Answer 95

- in response to raised pH, decreased CO2, decreased temperatures or decreased 2,3-DPG - also seen in hemoglobin F and hemoglobin variants - increased oxygen affinity

Answer 96

- in response to lowered pH, increased CO2, increased temperature, or increased 2,3-DPG - decrease in oxygen affinity

Answer 97

- A —> A1 and A2 - F - embryonic forms - each has a distinctive composition of polypeptide chains - Many other types of variant (abnormal) hemoglobin’s

Answer 98

Sickle cell anemia

Answer 99

- age - gender - pregnancy - altitude - smoking - associated disease - altered hemoglobin derivatives

Answer 100

1. Begins in the mitochondrion with the condensation of succinyl-CoA and glycine to form 5-aminolevulinic acid 2. Series of steps in cytoplasm produce corproporphyrinogen III, which re-enters the mitochondrion 3. Iron is inserted into the ring structure of protoporphyrin IX to produce heme

Answer 101

- recycling; an appropriate amount of iron is absorbed from the diet to compensate for losses and to main nontoxic amount in storage

Answer 102

- is a function of the rate at which the DNA code is transcribed into messenger ribonucleic acid (mRNA)

Answer 103

1. Alpha and Beta-globin polypeptides are translated from appropriate mRNAs 2. Once heme contain iron binds to each of the four polypeptide chains, the protein folds into a native 3D structure 3. The alpha and Beta units bind to each other by electrostatic bonding 4. An unstable intermediate encounter complex can rearrange the units to form a stable alphaBeta dimer 5. Two dimmers combine to form the functional hemoglobin molecule, an a2B2 tetramer

Answer 104

2 zeta 2 epsilon

Answer 105

2 alpha 2 epsilon

Answer 106

2 zeta 2 gamma

Answer 107

2 alpha 2 gamma

Answer 108

2 alpha 2 beta

Answer 109

2 alpha 2 delta

Answer 110

- rare autosomal recessive conditions - congenital erythropoietic porphyria

Answer 111

- lead poisoning

Answer 112

- a disease of heme metabolism in which a primary abnormality in porphyrin biosynthesis leads to excessive accumulation and excretion of porphyrin or their precursors by the biliary and/or renal route

Answer 113

- clinical presentation - source of enzyme deficiency - site of enzyme deficiency in the heme biosynthetic pathway

Answer 114

- neurological complications - skin problems - some have no symptoms

Answer 115

- acute neurological - nonacute cutaneous

Answer 116

Red wine color

Answer 117

Adding Ehrlich’s aldehyde reagent

Answer 118

- mitochondria becomes encrusted with iron and some granules exist around the nucleus - can be seen with Prussian blue stain

Answer 119

1. Storage: primarily ferritin in bone marrow macrophages and liver cells 2. Transport: with serum transferrin 3. Functional: as hemoglobin, myoglobin, and cytochromes

Answer 120

- normal iron status continues as iron intake lags behind iron loss, but eventually the loss will be too great from the intake to keep up —> depletion of iron stores —> iron deficiency anemia

Answer 121

- congenital defect: hereditary sex linked, autosomal (most males) - acquired defect: primary ; may evolve into acute myelogenous leukemia - association with malignant disorders: acute myelogenous leukemia, polycythemia vera, myeloma, myelodysplastic syndromes - secondary to drugs: isoniazid (INH), chloramphenicol; after chemotherapy - toxins, including alcohol, and chronic lead poisoning

Answer 122

- HFE gene related (type 1) - different mutations of the HJV gene responsible for juvenile hemochromatosis (or type 2 hemochromatosis) - Type 3 hemochromatosis is a different form of the disease that usually appears in midlife - Type 4 is related to the SLC40A1 gene that encodes for ferroportin

Answer 123

- when globin synthesis is impaired, protoporphyrin synthesis is correspondingly reduced - similarly, when porphyrin synthesis is impaired, excess globin is not produced - there is no fine regulation of iron uptake with impairment of either protoporphyrin or globin synthesis. - when globin production is deficient, iron accumulates in the cytoplasm of cells as ferritin aggregates

Answer 124

Thalassemias

Answer 125

- embryonic hemoglobins are primitive hemoglobins by immature erythrocytes in the yolk sac - include Gower 1, Gower 2 and Portland types - they are found in human embryo and persists until approximately 12 weeks of gestation

Answer 126

- Hemoglobin F is the predominant hemoglobin variety in the fetus and newborn - has two alpha and two gamma chains - appears by the 5th week of gestation and persists for several months after birth —> diminish to low levels, but constant levels throughout adulthood

Answer 127

- found in 95-97% - made up for two alpha and two beta chains - produced in uteri in small concentrations and converts to high concentrations 3-6 months after birth - subfraction of A is A1

Answer 128

- makes up 2-3% - made of two alpha chains and two delta chains - production begins shortly before birth and continues at a slow rate throughout the person’s life

Answer 129

- this subfraction can be termed glycolsylated hemoglobin and includes the separate hemoglobin fractions A1a, A1b, and A1C - formed during RBC maturation - 3-6% in normal person. - stable hemoglobin and is structurally the same as hemoglobin A except for the addition of a carbohydrate group as the terminal valine of the beta chain - the concentration of glycolsylated hemoglobin accurately reflects the patients blood glucose level

Answer 130

- carboxyhemoglobin - sulfhemoglobin - methemoglobin

Answer 131

- hemoglobin has higher affinity for carbon monoxide (200x) than oxygen does. - this results in oxygen deprivation and tissue necrosis if left untreated - normal levels: 1-3%

Answer 132

- the binding of hemoglobin to hydrogen sulfide produces an irreversible change in the polypeptide chains (produces green color) - this causes denaturation and precipitation of Heinz bodies - can combine with carbon monoxide and produce carboxysulfhemoglobin - can be formed by action of certain oxidizing drugs - normal: <1% - elevated = cyanosis

Answer 133

- hemoglobin with iron in the ferric state, instead of the ferrous state - results in poor delivery of oxygen. Cyanosis occurs with methemoglobin levels at greater than 10% and hypoxia at greater than 60% - normal: 2% produced per day

Answer 134

- typified by differing from normal hemoglobin only by the molecule that replaces oxygen - unable to transport oxygen - most cases are acquired

Answer 135

- dizziness - nausea - headache - muscular weakness

Answer 136

- sudden loss of consciousness - rapid death

Answer 137

Supplement oxygen

Answer 138

- usually results from mutant, codominant genes - mutant genes may be homozygous (such as SS in sickle cell disease) or heterozygous(such as SA in sickle cell trait) —> sickle cell gene may occur with C, E, or D giving rise to SC, SE, or SD disease

Answer 139

- amino acid valine at 6th position of the beta globin chain instead of glutamic acid

Answer 140

- hemoglobincyanide (cyanmethoemoglobin) (defunct) - alkaline electrophoresis - citrate agar electrophoresis - denaturation procedures - chromatography - molecular testing

Answer 141

- hemoglobin molecules in an alkaline solution have a net negative charge and move toward the anode

Answer 142

- screening procedure that separates Hgbs A, F, S, and C - fast hemoglobins are those that move furthest from the point of application —> include Hgb A, F, Barts, H and I - slow hemoglobins are those that move close to the application point —> include Hgb C, E, O and A2

Answer 143

- citrate agar separates hemoglobin fractions that migrate together on cellulose acetate— hgbs S, D, G, C, E and O - takes place at an acid pH

Answer 144

- in this method, Hgbs are separated on the basis of a complex interaction between hemoglobin, agar, and citrate buffer ions - due to similar migration patterns on cellulose acetate, all Hgb specimens that show an abnormal electrophoresis pattern in alkaline media should undergo electrophoresis pattern in alkaline media should undergo electrophoresis on acid citrate agar

Answer 145

Kleihauer-Betke

Answer 146

- denaturation test because we expose the specimen that denatures adult hemoglobin —> fetal hemoglobin (F) is resistant to acid lysis and therefore stays intact and stains pink with safranin —> adult Hgb (A) is susceptible to acid lysis and therefor will be faintly colored —> the number of fetal cells to adult cell is counted and a percentage is determined, which is compared to a reference range

Answer 147

- sensitization for HDN occurs when there is too much intermingling of fetal and maternal blood

Answer 148

- quantitation of hemoglobin A1 can be accomplished by cation exchange minicolumn chromatography - the results can be affected by several types of Hgb in addition to Hgb A1 - cellulose acetate and citrate agar electrophoresis should be used in conjunction with cation exchange chromatography to eliminate the possibility of interference by Hgb variants - other assay methods for glycolylated Hgb include high-pressure liquid chromatography (HPLC) and colorimetric methods

Answer 149

- gene deletions and mutations causing thalassemias and hemoglobinopathies can be identified using molecular testing - since Hgb (particularly the globin component) is maintained under genetic control, determining the genetic influence of hemoglobinopathies and thalassemias is beneficial

Answer 150

- the membrane becomes less flexible - the concentration of cellular Hgb increases - enzyme activity, particularly glycolysis, diminishes

Answer 151

Hemoglobincyanide

Answer 152

- using lysing agent in reagent solution to release Hgb from intact erythrocytes - free hemoglobin combines with potassium ferricyanide in the reagent. This converts Hgb iron state from ferrous to ferric form - intensity of color is proportional to the concentration of Hgb in the solution.

Answer 153

- when an erythrocyte is phagocytized and digested by the macrophages of the spleen, the hemoglobin molecule is disassembled - the resulting components are as follows —> iron —> protoporphyrin —> globin

Answer 154

- to be recycled by the red bone marrow in the manufacture of new hemoglobin

Answer 155

- catabolized in the liver into its constituent amino acids and enters the circulating amino acid pool

Answer 156

- is an alternate pathway for erythrocyte breakdown - this process normally accounts for less than 10% of erythrocytic destruction

Answer 157

- hemoglobin is released directly into the bloodstream and undergoes dissociation into alpha and beta dimers, which are quickly bound to the plasma globulin haptoglobin - haptoglobin binds to the alpha and beta dimers forming a haptoglobin-hemoglobin complex that prevents urinary excretion of plasma hemoglobin - the complex is removed by the liver and processed - thus in active intravascular hemolysis, the haptoglobin levels in plasma are low - once the haptoglobin is consumed, the alpha and the beta dimers are rapidly filtered by the glomeruli in the kidneys, reabsorbed a converted to hemoglobin

Answer 158

5 g per day - beyond this level, hemoglobin appears in the urine (hemoglobinuria)

Answer 159

- oxyhemoglobin (alkaline urine) - methemoglobin (acidic urine)

Answer 160

- becomes methemoglobin in circulation —> carrier: hemopexin —> excess binds to albumin to form methemalbumin

Answer 161

1. Hemoglobin alone, if hemolysis is severe 2. Excretion of hemosiderin by itself 3. Excretion of both hemosiderin and hemoglobin; if desquamated tubular cells contains hemosiderin granules

Answer 162

Heme Globin

Answer 163

- amino acid substitutions - diminished production of one of the polypeptide chains - homozygous A/A inheritance

Answer 164

Expels 2,3-DPG

Answer 165

Stronger acid

Answer 166

A shift to the right

Answer 167

A shift to the left

Answer 168

Decreased oxygen affinity

Answer 169

- mitochondria - vitamin B6

Answer 170

The mitochondria

Answer 171

- sulfhemoglobin

Answer 172

- substitution of a non polar amino acid residue for a polar reside near the surface of the chain

Answer 173

Hemoglobin F

Answer 174

- resists denaturation in the procedure

Answer 175

- variation in size: called anisocytosis - variation in shape: called poikilocytosis - alteration in color: suffix-chromia - inclusions in the erythrocytes - alterations to the erythrocyte distribution on a PB smear

Answer 176

- to mathmatically define cell size and the concentration of hemoglobin within the cell. —> Mean corpuscular volume (MCV) —> Mean corpuscular hemoglobin (MCH) —> Mean corpuscular hemoglobin concentration (MCHC)

Answer 177

- expresses the average volume (size) of an erytrhocyte - reference range: 80-96 fL (Hct/Rbc) x 10 = fL (femtoliters)

Answer 178

- expressed the average weight (content) of hemoglobin in an average erythrocyte. It is directly proportional to the amount of hemoglobin and the size of the erythrocyte - reference value is 27-32 pg (Hgb/RBC) x 10

Answer 179

- expresses the average concentration of hemoglobin per unit volume of erythrocytes. It is also defined ass the ration of the weight of Hgb to the volume of erthrocytes - reference range: 32-36% (Hgb/Hct) x 100 = g/dL or %

Answer 180

- average diameter of 7.2 um - range: 6.2-8.2 um - can also be classified by the MCV falling between 80-96 fL

Answer 181

- cells larger than leukocytes nucleus - >96 fL

Answer 182

- cells smaller than leukocyte nucleus - <80 fL

Answer 183

- general term for mature erytrhocytes that have a shape other than the normal round, bioconcave appearance on a stained blood smear, or variations - used cautiously

Answer 184

- significant in severe anemias

Answer 185

- megaloblastic anemias and macrocytic anemias (folic acid deficiency and pernicious anemia) - (hereditary lipoprotein deficiency)

Answer 186

- iron deficiency anemia - hemoglobinopathies

Answer 187

- Abetalipoproteinemia - cirrhosis of the liver with associated hemolytic anemia - following heparin administration

Answer 188

- pulmonary emboli in sickle cell anemia - microangiopathic hemolytic anemia

Answer 189

- variety of anemias - bleeding gastric ulcers - gastric carcinoma - peptic ulcers

Answer 190

Results from osmotic imbalance

Answer 191

- anemia associated with malignancy - Hb C disease - hemolytic anemias - iron deficiency anemia

Answer 192

- hemolytic anemias - thalassemias - myelofibrosis

Answer 193

- pointy irregular shaped projections that are unevenly dispersed around the red cell

Answer 194

- blister cells ruptured - looks like a bite out of the cell

Answer 195

- mechanical tearing of RBC - looks “ripped” - blister cells and keratocytes are generally grouped together under schistocytes

Answer 196

- also called echinocyte or crenated RBC - round projections evenly dispersed around the red cell

Answer 197

- cigar shaped - they represent a membrane defect in which the membrane is radically affected and suffers a loss of integrity

Answer 198

- oval or football shape

Answer 199

- fat crescent shape - irregular edges - remains after the rupturing of a blister cell - forms as a result of the physical process of fragmentation - these cell fragments are formed in the spleen and intravascular fibrin clots

Answer 200

- slightly larger - slightly bluer when stained with Wright’s stain

Answer 201

- also called drepanocytes - elongated, thin crescent - at least one end must be pointed - results from the gelation of polymerized deoxygenated Hb S.

Answer 202

- very round - no central pallor - have lost bioconcave shape - usually small than 6 um in size - occurs as the ratio of the surface area of the erythrocyte to the volume of the cell contents decreases because of the loss of the cell membrane. This loss creates membrane instability

Answer 203

- pallor is shaped as a slit - results from increase Na+ ion and decrease in K+ ion concentration within the cytoplasm of erythrocyte

Answer 204

- also called codocytes - have centers that look like targets

Answer 205

- also called dacryocytes - shaped like a tear drop - usually smaller than normal erytrhocytes

Answer 206

- moderately pinkish-red appearance with a light center when stained with a conventional blood stain

Answer 207

- the amount of Hgb present in the cell. - the lighter color in the middle, thinner portion of the cell does not normally exceed one third of the cell’s diameter and is referred to as the central pallor - ALSO can reflect state of cell immaturity

Answer 208

Variation of normal coloration

Answer 209

When central pallor exceeds one third of the cell’s diameter

Answer 210

Microcytic/hypochromic

Answer 211

- lacks the full amount of hemoglobin, and the blue color is caused by diffusely distributed residual RNA in the cytoplasm

Answer 212

- parasitic —> malaria, Babesia, leishmania - nonparasitic —> basophilic stippling (fine or coarse) —> Cabot rings —> Heinz bodies —> Howell-Jolly bodies —> pappenheimer bodies (aka siderotic granules)

Answer 213

- appears as tiny, round, solid staining, dark-blue granules. The granules are usually evenly distributed throughout the cell and often require careful examination to detect them

Answer 214

- sometime referred to as punctate stippling - these granules are larger than in the fine form and are considered to be more serious in terms of pathological significance

Answer 215

- stippling represents granules composed of ribosomes and RNA that are precipitated during the process of staining of a blood smear. - stippling is associated with clinically with disturbed erythropoiesis, lead poisoning, and severe anemias

Answer 216

- 0.2-2.0 um in size - can be see with a stain such as crystal violet or brilliant cresyl blue - must be a supravital stain - represents precipitated, denatured hemoglobin

Answer 217

- congenital hemolytic anemia - G6PD deficiency - hemolytic anemias - some hemoglobinopathies

Answer 218

- are round, solid-staining, dark-blue to purple inclusions (only one or two) - 1-2 um in size - are nuclear remnants predominantly composed of DNA and not seen in normal erythrocytes - this ruminant DNA is normally pitted out by the macrophages in the spleen, so the presence of H.J. Bodies are a sign of splenic dysfunction of absence

Answer 219

- also called siderotic granules - may be observed ubiquitous wright-stained smears as three to four purple dots aggregated in one area of the cell - are frequently seen in peripheral blood smears

Answer 220

- mitcochondria - ribosomes - iron particles

Answer 221

- iron-loading anemia - hyposplenism - hemolytic anemias

Answer 222

- probably identical structures - siderotic granules are dark-staining particles of iron in the erytrhocyte that are visible with a special iron stain— Prussian blue - siderotic granules can also be visualized around the nucleus in ringed sideroblasts in sideroblastic anemia, refractory anemia, and iron overload conditions

Answer 223

- the clumping of erythrocytes in a random, nonspecific arrangement - caused by the presence of antibodies reacting with antigens on the erythrocyte

Answer 224

- arrangement of erythrocytes in groups that resemble stacks of coins - is usually present in the thick portions of the normal blood smears. If the rouleaux exist in thin areas of the blood smear where the erythrocytes should just touch each other or barely overlap, pathological rouleaux are present - formation is associated with the presence of circulating cryoglobulins or paraproteins

Answer 225

- hemolytic anemia related to burns or prosthetic implants - renal transplant rejection

Answer 226

Sickle cell anemia

Answer 227

- ABO hemolytic disease of the newborn - acquired hemolytic anemias - blood transfusion reactions - DIC

Answer 228

- acute alcoholism - alcoholic cirrhosis

Answer 229

- hemoglobinopathies - Hb C disease - sickle cell - thalassemia

Answer 230

- homozygous beta thalassemia - myeloproliferative syndromes - pernicious anemias - severe anemia

Answer 231

Iron deficiency anemia

Answer 232

- rapid blood regeneration

Answer 233

- Howell-Jolly bodies

Answer 234

- basophilic stippling - Howell- Jolly bodies - reticulocytes - pappenheimer bodies - Heinz bodies

Answer 235

- basophilic stippling - cabot rings - Howel-Jolly bodies - polychromatophilia - pappenheimer bodies - Heinz bodies

Answer 236

- ring-shaped, figure-eight, or loop-shaped structures - stain red or reddish purple color - have no internal structure - represent remnants of microtubules from the mitotic spindle

Answer 237

- lead poisoning - pernicious anemia

Answer 238

- appears like rod shaped or angular opaque structures within some erythrocytes - found in Hb C disease

Answer 239

- most severe form of parasitic inclusions - has 3 life-threatening manifestations 1. Cerebral malaria 2. Respiratory distress 3. Severe malarial anemia - severe in kids and pregnant women - can cause hemolytic anemia

Answer 240

- plasmodium vivax - plasmodium falciparum - plasmodium malariae - plasmodium ovale * occurs in humans and mosquitos

Answer 241

- initiated when the female mosquito of anopheline mosquitoes bite an infected human - infected blood may contain male or female genotypes - female (macrogamecyte) matures into macrogamete - male (microgametocyte) undergoes maturation and results in production of microgametes - when male fertilizes female, it becomes a zygote (oocyte) - growth and development of oocyte results in production of large number of thread-like sporozoites,which circulate throughout the mosquito - sporozoites enter salivary glands of mosquito and are ready to be inoculated into the next bitten person

Answer 242

- species type - ambient temperature - can be 8-35 days long

Answer 243

- after being injected with sporozoites from infected mosquito, they leave the circulatory system within 40 minutes and invade the liver cells - all found species undergo an asexual multiplication phase. This provides thousands of tiny merozoites in each infected cell - rupture of infected liver cells releases merozoites into the circulation - schizogony - asexual cycle takes place within erythrocytes, results in 4-36 parasites on each infected erythrocyte

Answer 244

1. Sporozoite invades RBC 2. “Ring” stage of development 3. Ameboid stage of development 4. Asexual division 5. Cell rupture with release of spore; reinfection of RBC by some spores 6. Development of other spores into sexual forms 7. Development into egg and sperm cells after mosquito sucks them in 8. Fertilized cell developing into cyst 9. Ruptured cyst releasing sporozoites

Answer 245

- no symptoms until several continuous life cycles have been completed. - chills, followed by fever in a few hours - last 4-6 hours, and recur at regular intervals

Answer 246

- enlarged RBC - inclusions: schuffner dots, accole forms, signet-ring forms - cytoplam - blue discs with red nucleus - 12-24 merozoites

Answer 247

- Normal size - inclusions: Maurer dots - cytoplasm: minute rings, two chromatin dots, accole forms, gametes crescent shaped - 6-32merozoites

Answer 248

- normal size - inclusions: ziemann stippling - cytoplasm: one ring with one dot - 6-12 merozoites

Answer 249

- enlarged RBC - inclusions: schuffner dots - cytoplasm: one ring form - 6-14 one ring form

Answer 250

- most predominant species worldwide - within the first few hours after symptoms start, infected erythrocytes will contain trophozoites - Giemsa stain - single nucleus divides repeatedly - exhibits various stages in the asexual life cycle and many gametocytes in blood

Answer 251

- confined to the tropics and subtropics - advantages with group O - end may be pointed or rounded, elongated crease t or sausage shape - trophozoites and gametocyte are generally the only stages seen in peripheral blood

Answer 252

- occurs primarily in subtropical and temperate areas - all stages of development may be present on the peripheral blood smear

Answer 253

- widely distributed in tropical Africa and west African coast. Also has been reported in South America and Asia - all stages of development may be present on the peripheral blood smear.

Answer 254

- tick-born intraerythrocytic, protozoan parasite that can cause malaria-like symptoms and hemolytic anemia - resembles P. Falciparum - In humans, infections have been attributed to Babesia microti, derived from rodents - transmitted via blood transfusion

Answer 255

- humans are opportunistic hosts for Babesia when bitten by nymph or adult ticks. - Asplenic, elderly and immunocompromised patients are at greater risk for severe disease - found in North America, which includes northeastern and northwestern United States - particularity Long Island, New York, Nantucket, Martha’s Vineyard, MA

Answer 256

- Fever - hemolytic anemia - hemoglobinuria - capillary blockage/microvascular stasis may occur as a result of RBC fragments - RBC destruction leads to hemolytic anemia - elicits a T and B cell response. T is primary

Answer 257

- most important test to confirm is viewing blood smear - wright and Giemsa stains -after staining, reveals the ring forms of Babesiosis - also may demonstrate merozoites arranged in a tetrad configuration that resembles Maltese cross. - other tests include CBC count and erythrocyte sedimentation rate (ESR, usually elevated)

Answer 258

- Howell-jolly bodies - leukopenia - lymphopenia - thrombocytopenia

Answer 259

- Babesiosis has absence of pigment hemozin

Answer 260

- serum protein electrophoresis - liver function tests to look for elevated ALT, elevated alkaline phosphate level hyperbilirubinemia, and decreased haptoglobin levels

Answer 261

- IgM or IgG immune fluorescent assay - B. Microti titers

Answer 262

- found primarily in the cells of the mononuclear phagocytic system and may at times be seen in the circulating blood in large mononuclear cells. - burst out of macrophages with characteristic nucleus and kinetoplast

Answer 263

- include the hemoflagellates, contains two genera that parasitize humans - seen in circulating blood the cardiac muscle and CSF

Answer 264

Megalocytes

Answer 265

Microcytes

Answer 266

Drepanocyte

Answer 267

- fragments of erythrocytes

Answer 268

- compact round shape

Answer 269

- acanthocytes

Answer 270

- sickle cells

Answer 271

- polychromatophilia

Answer 272

Granules composed of ribosomes and RNA

Answer 273

- aggregates of iron, mitochondria and ribosomes

Answer 274

- precipitated denatured hemoglobin

Answer 275

P. Falciparum

Answer 276

- are inherited single-gene disorders that affect the amino acid residual sequence or production of normal hemoglobin - patient will demonstrate an alteration of hemoglobin distribution - encompasses a heterogenous group of disorders associated with genetic mutations in both the alpha-globin and beta-globin genes. - gene mutations in these genes produce qualitative protein changes; patient produces Hgb S, C, D, G, E, etc (instead of Hgb A, A2 or F)

Answer 277

- overall zygosity and quantity of Hgb produced

Answer 278

- either the homozygous occurrence of the gene for the abnormality OR the possession of a heterozygous, dominant gene that produces a hemolytic condition

Answer 279

- as the heterozygous and normally asymptomatic state - example: sickle cell anemia trait must be inherited from both parents

Answer 280

- SCD and B-thalassemia - they are found in the “malaria belt” that extends through the Mediterranean and sub-Saharan African through Southeast Asia and Southern China - These hemoglobin mutations occur at high incidences in these regions because heterozygous have have selective advantage against infection with P. Falciparum

Answer 281

- estimated 7% of world population Carries a globin-gene - majority of the cases is inherited as an autosomal recessive trait. Disease associated with autosomal recessive genes need to be in the homozygous state to produce disease - some are caused by inheritance of an autosomal dominant gene that will produce hemolytic disease in its heterozygous state - may have hemolytic manifestations - 25% demonstrate decreased red cell survival due to red cell membrane deformity that characterizes hemolytic disease

Answer 282

- inherited or genetic defects related to hemoglobin

Answer 283

- abnormal molecular structure - a defect in the rate of synthesis - disorders that are a combination of both

Answer 284

- one of more of the polypeptide chains of globulin in the hemoglobin molecule, for example, sickle cell anemia - includes: —> Hb SS (SCD) —> Hb SA (sickle cell trait) —> Hb C (disease or trait)

Answer 285

- one or more particular polypeptide chains of globulin in the hemoglobin molecule - includes: —> beta and alpha thalassemia

Answer 286

- Hb A —> 95-98% - Hb A2 —> 2-3% - Hb A1 —> 3-6% - Hb F —> <1%

Answer 287

- a general term for abnormalities of hemoglobin structure in which the sickle gene is inherited from at least one parent - characterized by the production of of Hb S, anemia and acute and chronic tissue damage secondary to the blockage of blood flow produced by abnormally shaped RBCs -

Answer 288

- the most common form of hemoglobinopathy - expression of inheritance of sickle gene from both parents.

Answer 289

- from coinheritance of the sickle gene - common variants include Hb SC disease and Beta-thalassemia

Answer 290

- sickle cell gene must be inherited from both parents in the sickle cell anemia

Answer 291

- a single nucleotide change (GAT to GTT) that results in the substitution of valine got glutamic acid at the sixth position on the Beta chain of the hemoglobin molecule

Answer 292

- abnormalties in polymerization (or gelation), with deoxygenation that leads to sickling - the end results of the polymerization is a permanently altered membrane protein. Two-thirds of the RBCs are removed by extravascular mechanisms

Answer 293

- found mostly in persons of African ancestry, but it also affects persons of Mediterranean, Caribbean, South and Central American, Arab and East Indian ancestry - sickle cell carrier state confers a selective advantage of P. Falciparum malaria, because of preferential sickling of only the parasitized cells. The prevalence of the disease in some regions reflects this selective advantage or protective mechanism

Answer 294

- polymerization of Hb S occurs under conditions of extremely reduced oxygen and increased acidity in the blood - sickling is promoted by low oxygen tension, low pH, increased 2,3- diphosphoglycerate, high cellular concentration of hemoglobin, loss of cell water, Hb C and Hb O-Arab - sickling is retarded by Hb A, Hb F (at least 30%), Hb J, and alpha thalassemia

Answer 295

- increased MCHC in proportion to the number of moelcules in the deoxygenated state - deoxyhemoglobin S is less soluble than deoxyhemoglobin A or oxyhemoglobin S

Answer 296

Deoxygenation

Answer 297

- first stage progresss from the formation of small amounts of polymer to larger amounts of highly ordered polymer as the result of severe and prolonged deoxygenation. This polymerization produces the resultant sickling - because cells that have large amounts of ordered polymer may be caught in capillaries and cause obstruction of vessel - this initiates a pattern of blood not flowing properly to the tissue and creating lack of oxygen. - lack of oxygen causes more sickling and more deprivation of oxygen to tissues. This can cause intense pain and tissue necrosis - decreased oxygen tension of the spleen makes it vulnerable to tissue necrosis after vasoocclusion . This causes splenic dysfunction and the presence of Howell-Jolly bodies in mature RBCs

Answer 298

- they return to their normal shape. Repeated cycles of sickling and unsickling lead to the RBCs becoming permanently damaged - this process ends in hemolysis, which leads to anemia - in addition, repeated episodes of this type lead to the necrosis of body tissues

Answer 299

Reversibility - produces reversible sickles which are more boat shaped

Answer 300

- diminished and production of irreversible sickles ensues. - this is sign of poorer prognosis for the patient as they become resistant to treatment.

Answer 301

- serpentine-like - more slender with pronounced pointed ends

Answer 302

- the adherence of sickled erythrocytes to the vascular endothelium may contribute to painful vasoocculation - patients have increased susceptibility to opportunistic infections

Answer 303

- fever - acute pain - dehydration - cyanosis - extreme sensitivity to opportunistic infections - can lead to organ and tissue failure

Answer 304

- caused by recurrent obstruction of the microcirculation by intravascular sickling

Answer 305

- can lead to organ or tissue failure

Answer 306

- significant activation of coagulation with consequent increase in fibrinolysis

Answer 307

- enlargement of the heart - progressive loss of pulmonary or renal function - stroke - arthritis - liver damage - other complications

Answer 308

- splenic dysfunction is a life-threatening complication that develops during infancy - infant is vulnerable to to shock and infection from encapsulated bacteria due to the sickles getting trapped in the spleen - symptoms appear 6 months after birth - vasoocclusive disease develops between 1-6 years - development and growth delays - destruction of bone and joints with ischemia and infraction of the spongiosa

Answer 309

- no increase disease manifestations - but there is an increase in maternal mortality of 20% and fetal mortality of 20%

Answer 310

- SS homozygotes have severe HA with Hct values between 15-30% - RBCs with low Hb F have shortened life span - erythropoietic suppression is caused by: aplastic tissue or megaloblastic erythropoiesis - acute chest syndrome is a significant cause of death - higher blood viscosity that leads to complications

Answer 311

- shoulder and hip abnormalities - mutliorgan dysfunction - pain - pigmented gallstones in 30-60% of adults - papillary necrosis - leg ulcers

Answer 312

- hallmark of the disease and most common complaint - vasoocclusive crises are predominantly what send patients to the hospital - high-dose methylprednisolone decreased pain duration in children

Answer 313

- atelectasis and infiltrates - thoracic bone infarction is common in hospitalized SCD patients with acute chest pain - incentive spirometry can prevent atelectasis

Answer 314

- 24% of patients have a stroke by 45 years of age - cerebral infarction in SCD is associated with an occlusive vasculopathy involving the distal intracranial segments of the internal carotid as well as the proximal middle and anterior cerebral arteries - blood transfusions decrease stroke rise by should be used with prudence due to: —> alloimmunization —> iron overload —> transfusion withdrawal -

Answer 315

- C, E, and D, giving rise to SC, SE, and SD disease

Answer 316

- Hb S-Hb C - Hb S-Beta thalassemia

Answer 317

- Hb S is deoxygenated, it becomes polymerized and produces sickling

Answer 318

- in addition to decrease Hgb, Hct, and RBC cell count, persistent increase of WBC count of 12,000 to 15,000 x 10^9/L is common - Reticulocytoisis (8-12%) - increased MCV to levels up to 100 fL - elevated serum: unconjugated bilirubin and methemalbumin - descreased serum haptoglobin and hemopexin - increased serum lactate dehydrogenase (LDH) - Mildly increased aspirate transaminase (AST) - increased urine urobilinogen

Answer 319

- morphology on peripheral blood smear can include moderate to significant: —> anisocytosis —> poikilocytosis —> hypochromia - red cell abnormalities —> target cells —> microcytes —> polychromatophilia —> basophilic stippling - Howell-Jolly bodies may be present if hyposplenism is present - if patient is in acute crisis state, sickled red cells may be seen on peripheral smears

Answer 320

- thin later isoelectric focusing (IEF) - High pressure liquid chromatography (HPLC) - Globin DNA analysis (costly and limited in what it can identify)

Answer 321

- reassessment of the hemoglobin phenotype - measurement of hemoglobin concentration and red cell indices - inspection of red cell morphology - correlation with the clinical history

Answer 322

- Hb S —> 80-95% - Hb F —> 0-20% - a normal amount of Hb A

Answer 323

- electrophoresis at acid and alkaline pH has been used for years - cation-exchange HPLC is emerging as method of choice of quantification of Hb A2 and Hb F and ID Hgb variants

Answer 324

- All cases of SCD can be diagnosed by direct DNA analysis by PCR - most cases of thalassemia can be diagnosed by direct analysis by PCR

Answer 325

- important because of the high frequency of SCD - fetal diagnosis can be made by amniocentesis at about the 14th week of gestation - the current widespread use of chorionic villus biopsy allows DNA diagnosis to be performed at the 7th-10th week of gestation

Answer 326

- principle Hgb is Hb F - distribution is 80% of Hb F and 20% is beta-globin - During last trimester, there is a progressive increase in beta-globin synthesis and a decrease in y-chain synthesis - approximately 80% of the non-alpha globulin is y-globin and 20% is beta-globin

Answer 327

- the initiation of prophylactic antibiotics and pneumococcal conjugate vaccination by 2 months of age, children with sick cell anemia are vulnerable to life threatening pneumococcal infections

Answer 328

- screenings will ID approximately 50 sickle cell carriers for every infant diagnosed - confirmatory tests should occur no later than 2 months of age - blood collection on first day does not pose a threat to - sample is collected onto a filter paper from a heelstick. Remains stable for at least 1 weeks at room temperature. Extremely premature infants may have false positive - most state based screening programs use either thin-layer IEF or HPLC as initial screenings on capillariy blood collected from heelstick and absorbed onto a filter paper

Answer 329

- infant with sickle cell traits (SA) has both normal beta genes and a beta S gene - will have predominance of Hb F and both Hb A and Hb S. - There will always be more Hb A than Hb S in these infants because alpha chain preferentially pair with normal beta chains

Answer 330

- monitoring the severity of the anemia and transfusing blood only when necessary - treating acute and chronic pain according to a rational guideline - diagnosing organ failure and administering appropriate therapy; over time, recurrent vasoocclusion and its associated vascuopathy result in significant progressive Organ failure

Answer 331

- bone marrow transplant offer the only potential cure for sickle cell anemia - general suppurative care includes daily oral folate supplementation, antibiotic prophylaxis in childhood, pneumovax, haemophilus influenza vaccine, meningococcal vaccine, a yearly flu shot, a yearly eye examination, prompt treatment of infections, and avoidance of dehydration

Answer 332

- gene therapy - butyric acid - clotrimazole - nitric oxide - Nicosan

Answer 333

- inserting a normal gene or turning off the defective gene in SCD patients

Answer 334

- food additive that may increase Hb F

Answer 335

Over the counter anti fungal medication that helps prevent water loss and mitigate sickle formation

Answer 336

- inhibits vasoconstriction of the blood vessels to prevent vascoocclusive crises

Answer 337

- herbal treatment in early trials that prevents sickle crises; originally used in Nigeria, West Africa

Answer 338

- prevention

Answer 339

- pneuomococcal - influenza A - H. Influenzae

Answer 340

- to minimize splenic sequestration and autosplenectomy

Answer 341

- improve oxygen-carrying capacity and transport - dilute circulating sickle cells to microvascular perfusion

Answer 342

- Hb less than 5 g/dL with significant signs of anemia and hypoplasia - Angina or high-output failure - acute hemorrhage - acute CNS complications - acute chest syndrome with hypoxia - sequestration crisis - preoperative preparation

Answer 343

Disease control

Answer 344

- Hydroxyurea, a ribonucleotide reductase inhibitor, stimulates the production of Hb F but suppresses bone marrow production - Fetal hemoglobin is a potent inhibitor of the polymerization of deoxyhemoglobin S

Answer 345

- increase the production of Hb F - improve RBC hydration - increase the availability of of the nitric oxide - possess anti-inflammatory effects

Answer 346

- nitric oxide - anti-inflammatory agents, such as statins - anticoagulants and antiplatelet agents

Answer 347

- genetic counseling may be useful in the prevention of sickle cell anemia - when the parents are both Hb SA (Carriers), antenatal diagnosis can be performed during the 18th to 20th weeks of pregnancy by analyzing DNA from amniotic fluid - experimental therapy includes induction of Hb F b the short-chain fatty acids (FA) and membrane-active drugs —> short chain FA appear to modulate gene expression directly by interacting with transcriptionally active elements of the genes

Answer 348

- % of Hb S —> 80-98% - % of non-S Hb —> 2-15%(fetal) - clinical severity: 3-4 - 10-20% reticulocytosis - rare splenomegaly

Answer 349

- % Hb S —> 60-90% - % non-S Hb —> 10-30% - clinical severity: 1-3 - splenomegaly - microcytosis - 4+ target cells

Answer 350

- % Hb S —> 50% - % non- S Hb —> 50% (Hgb C) - clinical severity: 1-3 - splenomegaly - 4+ target cells

Answer 351

- % Hb S —> 30-40% - % non-S Hb —> 60-70% (Hgb A) - clinical severity: 0 - normal morphology - no splenomegaly

Answer 352

- inheritance of the sickle gene from one parent and Beta thalassemia from the other parent -can be diagnosed by examining the blood film and through hemoglobin electrophoresis - blood film reveals hypochromic, microcytic red cells with polychromatophilia, target cells, stippling and rarely sickled cells - electrophoresis reveals that 60-90% is Hb S and 10-30% is Hb F - spleen remains functional but retinopathy is more common

Answer 353

- patient have only Hb S and C with an absence on Hb A and normal or increased levels of Hb F. - 50% of cells are target cells on blood smear - spleen remains functional - experience mild to moderate hemolytic anemia and usually have splenomegaly

Answer 354

1. In SC RBC, the intracellular hemoglobin concentration is significantly elevated because of the presence of Hb C 2. SC RBC have atleast a 10% higher level of Hb S than do SA red cells.

Answer 355

- retinopathy - hematuria from medically infarcts - aseptic necrosis of the femoral head

Answer 356

- approximately 8% of Black Americans are heterozygous for Hb S - provides a survival advantage over individuals with normal hemoglobin on regions where malaria, P. Falciparum, is endemic - sickling crises very rare - electrophoresis of whole blood reveals that 35-45% of hemoglobin in patients with sickle cell trait is Hb S

Answer 357

- hematuria - splenic infarction At high altitudes - hyposthenuria - bacteriuria - pyelonephritis in pregnancy

Answer 358

- growing global health problem - Hb E-Beta thalassemia and Hb H disease account for much of the projected increases in thalassemia - Hb E-Beta thalassemia is one of the most frequent hemoglobinopathies - Hb E is 60% of the population in Southeast Asia - Prevalence is growing rapidly along the coastal regions of North America - Alpha Thalassemia, often considered benign, is now recognized to be more severe than originally reported

Answer 359

- by an abnormality in the rate of synthesis of the globin chains. This is in contrast to an inherited structural defect in one of the globin chains that produces hemoglobin with abnormal physical or functional characteristics

Answer 360

- autosomal - whether it is autosomal dominant or recessive is questionable because heterozygotes are not always symptomatic

Answer 361

- Nonsense mutation leading to early termination of the globin chain - mutation in one of the noncoding intervening sequences of the original globin chain gene, which causes inefficient splicing to mRNA - mutation in the promoter area that decreases the rate of gene expression - mutation at the termination of the gene that leads to lengthening of the globin chain with additional amino acids rendering the mRNA unstable - total or partial depletion of a globin gene, probably due to unequal chromosomes crossing over

Answer 362

- characterized by the absence or decrease in the synthesis of one of the two constituent globin subunits of a normal hemoglobin molecule - can be classified as alpha r beta depending on the affected subunits -

Answer 363

- zygosity - quantity of Hgb produced

Answer 364

- have higher severity than beta thalassemia since alpha chains comprise all normal hemoglobin fractions - decreased synthesis of alpha globin in accelerated red cell destruction because of the formation of insoluble Hb H inclusions in the mature erythrocyte

Answer 365

- one of the most common single-gene disorders - overall quantity of A1 is diminished, which is compensated by an increase in gamma and delta chain production - the more severe beta thalassemia reflects the extreme insolubility of alpha globin, which is present in excess in the red cells because of decreased B-globin synthesis - 200+ point mutations in/around Beta-globin gene are known to cause unstable alpha-globin chains —> ineffective erythropoiesis now appears to be caused by accelerated apoptosis - rarely by deletion

Answer 366

- that many patients with alpha thalassemia have a defect in RNA processing. This defect affects efficient RNA splicing during protein globin synthesis

Answer 367

- decreased Hgb, Hct abd red cell count - Hgb concentration can be as low as 2-3 g/dL in homozygous patients - red cell indices are significantly reduced - RDW is increased because of anisocytosis - increased reticulocytes formation 5-10% - decreased osmotic fragility - moderately increased bilirubin - increased serum iron - saturated total iron-binding capacity (TIBC)

Answer 368

- anisocytosis - poikilocytosis - microcytic (significantly) - hypochromic (significantly) - target cells - polychromatophilia - few to many nucleated red cells

Answer 369

- increased Hb F and decreased Hb A

Answer 370

- no Hb A - increased Hb A - decreased Hb F - the absence of Hb A is owing to the absence of Beta-chain synthesis

Answer 371

- could be mistake for a mild iron deficiency anemia on a peripheral blood smear - decreased MCV - increaesed Hb A2 on electrophoresis - decreased osmotic fragility

Answer 372

- ideally is conducted in the first trimester of pregnancy using chorionic villus tissue for DNA analysis by PCR to detect point mutations or deletions - later, second trimester fetal blood analysis is done to estimate relative rates of synthesis of globin chains of hemoglobin. This is performed to estimate relative rates of synthesis of globin in mid-trimester fetuses and base the diagnosis on the beta-to-alpha (B/a) biosynthetic ratio

Answer 373

- most newborn screening programs employ HPLC or IET as the preferred first-line technique to make a presumptive diagnosis of a clinically significant hemoglobinopathy - if an abnormal is identified, ethnicity information and parental studies are helpful in guiding the sequence of diagnostic tests for specific hemoglobinopathies

Answer 374

- severe anemia requires blood transfusion - bone marrow or PSC transplant - frequent transfusion cause iron overload —> address with iron chelators (3)

Answer 375

1. Deferiprone 2. Deferoxamine 3. Deferastox (newest) - combined use of deferiprone and deferoxamine are effective at improving cardiac function and patient QoL.

Answer 376

- careful counseling - prenatal diagnosis in Sardinia reduced incidence of homozygous Beta thalassemia by more than 90%

Answer 377

- deletion that removes one or both alpha-globin genes from the affected chromosome 16

Answer 378

- basis of genotype and the total number of abnormal genes that result

Answer 379

- silent carrier state (one inactive/deleted alpha gene) - alpha thalassemia trait (two inactive/deleted alpha genes) - Hb H disease (three inactive/deleted alpha genes) - alpha thalassemia major; Hydrops fetal is with Hb Bart (four inactive/deleted alpha genes)

Answer 380

- this hemoglobinopathy is prevalent in the same geographic area as Hb S (sickle cell) disease - Hb C differs from Hb A by the substitution of a single amino acid residual lysine, for glutamic acid in the 6th position from the amino (NH2) terminal end of the Beta chain. This is the exact point of substitution of Hb S; however, the amino acid is different - normally NC/NC - 50% target cells on peripheral blood smear - mild, chronic hemolytic anemia with associated splenomegaly

Answer 381

- results from the inheritance of one gene for Hb S from one parent and one gene for Hb C from the other parent. - the course of this disease is generally milder than SCD, although Hb C tends to aggregate and potentiate the sickling of Hb S - symptoms similar to mild sickle cell anemia

Answer 382

- target cells - folded erythrocytes - intracellular crystal

Answer 383

- Hb D has several variants - patients who are homozygous or heterozygous are asymptomatic - some target cells may be seen on the examination of peripheral blood smear - Hb D migrate to same position as Hb S and Hb G at alkaline pH - migrate to same position as Hb A at acid pH

Answer 384

- occurs with the greatest frequency in Southeast Asia - Hb E/Beta thalassemia is worldwide clinical problem - In Thailand, frequency is 50% - appear in both homozygous and heterozygous forms and as compound heterozygotes in combination with alpha, beta thalassemias, and other structural variants - results from substitution of lysine for glutamic acid in the beta chain of hemoglobin - clinical presentation is diverse. Can range from entirely asymptomatic to mildly to severely anemic

Answer 385

- mild to severe chronic hemolytic anemia - most frequently results from an absence of three of the four alpha-globin genes - primarily affects individuals throughout Asia, the Mediterranean islands, and parts of the Middle East - because of the large influx of immigrant from SouthEast Asia in the past 20-30 years, Hb H has increased significantly - Hb H migrates at a fast rate at alkaline pH during Hgb electrophoresis

Answer 386

- methemoglobinemia is a disorder associated with elevated methemoglobin levels in the circulating blood - causes of methemoglobinemia include acquired toxic substances, Hb M variants, and NADH-methemoglobin reductase (also called diaphorase) deficiency - Hb M has five variant forms. It displays a dominant inheritance resulting from a single substitution of an amino acid in the globin chain that stabilizes iron in the ferric form. NADH-disphorase is the enzyme that reduces cytochrome b5 which converts naturally occurring ferric iron back to the ferrous state

Answer 387

- hemoglobin variants in which amino acid substitutions or deletions weaken the binding forces that maintain the internal portion of the globin chains of the Hgb molecule - most are inherited as autosomal dominant disorders -

Answer 388

- denature and precipitate in erythrocytes such as Heinz’s bodies of an oxidizing drug or an infection. - Heinz bodies are associated with alpha or beta chain abnormalities. Tetramer of normal chains, such as Hb Bart and Hb H, appear in thalassemias

Answer 389

- retention of Hb F into adult life is abnormal - it is a benign condition in which significant Hb F production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced - the level of expression is 15-30% of total hemoglobin

Answer 390

- Hb H disease associated with myeloproliferative or myelodysplastic disorders - Hb H disease associated with mental retardation

Answer 391

- incompatible with life - affected fetuses die either in utero or shortly after birth

Answer 392

- no symptoms - laboratory findings include target cells and possibly mild hypochromia

Answer 393

- Hb H migrates as a fast rate at alkaline pH during Hgb electrophoresis - results similar to iron deficiency anemia, except RBC count and RDW are usually greater and the MCV is lower. - retic count is 5-10% but may be within normal range - Serum ferritin can be normal or elevated

Answer 394

- target cells - ansiocytosis - poikilocytosis - polychromasia than in patients with iron deficiency

Answer 395

- mild anemia - microcytosis - abnormal RBC morphology - splenomegaly

Answer 396

- moderate anemia - ineffective erythropoiesis - microcytosis - abnormal erythrocytes morphology - splenomegaly - iron overload - not transfusion dependent

Answer 397

* also called Cooleys anemia - severe anemia caused by ineffective erythropoiesis - transfusion dependent - organ damage (heart and liver) secondary to iron overload - extramedullary erythropoiesis - hepatosplenomegaly

Answer 398

- heterozygous and asymptomatic

Answer 399

- a change of a single nucleotide (GAT to GTT) - the substitution of valine for glutamic acid at the sixth position on the beta chain of the Hgb molecule

Answer 400

- sickle cell disease

Answer 401

- drepanocytes

Answer 402

- extremely reduced oxygen - increased acidity in the blood

Answer 403

- severe transfusion-dependent anemia

Answer 404

Iron overload

Answer 405

Hb A levels normal

Answer 406

- decreased solubility - the ability to form intracellular crystals

Answer 407

- inherited autosomal dominant disorders - results from Amino acid substitutions or deletions - are hemoglobin variants

Answer 408

- four heme groups - two alpha globin chains - two beta globin chains

Answer 409

Expels 2,3-DPG

Answer 410

- Heinz bodies

Answer 411

Howell-Jolly bodies

Answer 412

Basophilic stippling

Answer 413

- electrophoresis - solubility testing - denaturation of hemoglobin (acid or alkaline)

Answer 414

Women - 12-16 mg/dL Men- 14-18 mg/dL