Hematology Unit 1 BL class of 2019 Flashcards Preview

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Flashcards in Hematology Unit 1 BL class of 2019 Deck (299):
1

hematology is concerned with what in relation to blood?

nature, function, diseases

2

what are the 3 major types of cells in blood?

erythrocytes (RBC), leukocytes (WBC), platelets

3

peripheral blood is what?

blood flowing through arteries and veins

4

what is hematopoiesis?

the making of blood in marrow from hematopoietic stem cells, differentiation of development, production of all types of blood cells

5

cellular component of blood makes up _______-______% of its volume.

40-45%

6

what is the rest of blood (the liquid stuff) called?

plasma

7

what do you need to do to blood when drawing for tests?

know if plasma or serum is needed and what anticoagulant you need

8

list the components of plasma, buffy, and RBC layers of blood samples.

Plasma is in the plasma, buffy is WBC and platelets, then RBC

9

erythrocytes

bulk of cellular blood. lack nucleus, lack mitochondria. contain mucho mucho hemoglobin. 120 day life span. 175 billion made per day.

10

hemoglobin

tetrameric protein, reason RBCs are red. most has 2 alpha globulin chains and 2 beta globulin chains—>Hemoglobin A. each of the tetramers are bound to a heme prosthetic group

11

mutations in hemoglobin can lead to:

molecules that bind O2 less well, unstable molecules (premature breakdown—hemolysis), polymerization into long chains/crystals, abnormally shaped/fragile cells

12

hemoglobin S

most common mutation in RBC, leads to sickle cell disease. glu—>val at 6th position in beta globin chain

13

imbalances in alpha or beta globin chains lead to ______.

thalassemias

14

what is porphyria?

mutations in enzymes involved in synthesis of heme prosthetic group

15

what type of metabolism do RBCs depend on?

anerobic

16

mutations in genes coding for enzymes needed for anaerobic metabolism cause _______.

hemolytic anemia. most common version is G6PD (x linked, 15% of african male population). G6PD is most common human enzyme defect.

17

why are RBC’s shaped like a biconcave disc?

provides 40% more surface area than sphere with same volume, allowing for more gas exchange. allows them also to squeeze into different shapes due to ratio. allows them to move through/be culled in endothelium of the spleen

18

what allows the RBC to be deformable and still maintain its structural integrity?

a 2D elastic network of cytoskeletal proteins tethered to cytoplasmic domains on the transmembrane proteins in the membrane.

19

what substrates does bone marrow need to make RBCs?

iron (can be decreased due to diet, blood loss, etc.), vit. B12 and folic acid, erythropoietin

20

what are the 5 WBCs:

lymphocytes, neutrophils (PMNs), monocytes, eosinophils, basophils

21

lymphocytes

key players in adaptive immune response (development of memory after exposure to an infectious agent)

22

innate immunity

protection against infection that relies on pre-existing mechanisms. capable of rapid response

23

neutrophils

WBC responsible for finding, ingesting (phagocytosis), digesting bacteria, cell debris, dead tissue. 7 hours half life in peripheral circulation. 70 billion made per day.

24

malignancies arise from cells of _______ origin.

hematopoietic. all are clonal, neoplastic (cells have undergone several mutations altering proliferative/differentiation capacity). some are classic mutations (translocations, etc.) others have no characteristic cytogenetic abnormalities

25

lukemia

malignant cells from bone marrow are in the bloodstream

26

lymphomas

extramedullary collections of malignant lymphoid cells (involving lymph nodes or organs)

27

what are the two classifications of lukemia?

acute or chronic. acute=cells are immature, progression is rapid. chronic=cells are more mature, more indolent course

28

hemostasis

arresting of bleeding, allows blood to clot in response to damaged vessels. due to platelets. results from complex interactions btw platelets, endothelial lining of bv, and coagulation factors in response to endothelial disruption

29

how many platelets can a megakaryocyte produce?

5000

30

complete blood count began as what?

a measurement of Hg and cellular components of peripheral blood.

31

hemoglobin is measured where?

in vitro-RBC is lysed and Hg is converted to a spectrometer friendly form. most techniques use cyanmethhemoglobin (absorbance=525/540nm). shows a linear relationship btw light absorption and concentration of a sample

32

hematocrit is a measure of what?

how much of a sample is occupied by RBCs. is a %. done with formula: %=RBCxMCV

33

physiologic variables affect one’s RBC’s include what 3 things?

age, sex, altitude

34

aperture impedance

Coulter principle. Counts RBC, WBC, platelets. an electrical current is run across an aperture of known size—>cell or particle passes through—>current flow changes—>voltage surges—>surge size tells you what size it is. number of pulses tells you how many cells/particles. measures size of nucleus and cytoplasmic granularity

35

what are the x and y axes of an aperture impedance histogram?

x=range of pulse magnitudes, y=number of events

36

what can cause inaccuracy in aperture impedence

multiple cells enter at once

37

light scattering techniques

collect forward, narrow/wide angle scattered light. estimates size of a cell based on the scatter (measures cross sectional diameter).

38

erythrocyte indices

calculations for size, content, Hgb concentration of red cells. can help characterize anemias. Healthy=little variation.

39

Mean Corpuscular Volume (MCV)

average volume of red cells. derived from height of voltage pulse, calculated with Hct=MCVx RBC (RBC and HCT are determined manually—> HCTx10/RBC)

40

mean corpuscular hemoglobin

MCH is weight of Hgb of average red cell. calculated from MCH=Hgb/RBC

41

mean corpuscular hemoglobin concentration (MCHC)

average concentration of Hgb in a volume of packed red cells. MCHC=(Hgb/Hct)x100

42

Red cell distribution width (RDW)

measure of variation in size of red cells and is proportional to the width of the measured histogram

43

reticulocytes

immature, anucleate RBC that still have RNA, ribosomes, organelles (enable continued Hg production). Bone marrow 3-4 days—>released to peripheral blood 1-2 days—> lose RNA and organelles—>mature RBC

44

what stains RNA, ribosomes, organelles in the reticulum?

Supravital staining (brillant cresyl blue, methylene blue)

45

nucleated RBCs

nucleated RBCs/100 WBCs

46

what is thrombocytopenia?

too few platelets

47

what is thrombocytosis?

too many platelets

48

what is thrombocythemia?

neoplastic expansion of platelets

49

optical platelet counting

high angle and low angle scatter signals are combined fore each cell. transformed into volume plotted on vertical axis/refractive index values on horizontal to give a platelet scattergram

50

combination of impedance and optical counting

impedance channels are used as defaults, but a fluorescent channel is backup when there is an abnormality.

51

platelet measurements are made how?

forward scatter for size, side scatter for internal structure, fluorescence for RNA/DNA stain

52

labeled-platelet counts

counted by measuring green fluorescence form FITC on monoclonal antibody in a reagent. Binds the CD61 antigen found on all normal platelets. useful when there’s lots of RBC/WBC fragments

53

when do white cell counts and differentials stop varying/changing?

after puberty

54

what is a sheath flow-based counting system?

enable passage of single cells through a sensing zone where multi-parameter analysis can happen when several sensors info is combined

55

flow cytometry and light scatter for WBC counts

determined with flow cytometry+semiconductor laser. cell info is obtained with forward light scatter for volume, lateral for internal structure, fluorescent light for RNA/DNA info. produces scattergram

56

cytochemistry and light scatter

peroxidase channel uses cytochemical rxn to produce black rxn. product. neutrophils, eosinophils, monocytes, lymphocytes fall into 4 clusters (separated by electronic thresholds)

57

what is a blood smear made from?

EDTA anti coagulated blood to prevent artifact. observe at low then high power.

58

what is red cell morphology on a smear?

little size/shape variation, well spread,

59

White cell morphology on a smear?

concentrated at the end of the film

60

neutrophils morphology

acidophilic with fine granules, clumped chromatin in nucleus divided into 5 lobes. too few lobes-neutropenia. too many lobes-neutrophilic.

61

lymphocyte morphology

scant cytoplasm, round nucleus, dense chromatin. most abundant WBC from age 2-8. too few=lymphopenia, too many=lymphocytosis

62

monocyte morphology

largest cells, irregular lobulated nucleus, ample grey-blue cytoplasm, azurophilic granules, outline of cytoplasm is irregular, vacuoles. too few=monocytopenia, too many=monocytosis

63

eosinophil morphology

larger than neutrophils, bi-lobed nucleus, larger spherical granules, count is constant in life. too many=eosinophelia

64

basophil morphology

similar in size to neutrophils, nucleus obscured by purple-black-coarse granules, least abundant. too many=basophilia

65

anemia

insufficient RBC mass to deliver oxygen to peripheral tissues. defined by measuring hemoglobin concentration (Hgb), hematocrit (Hct), RBC

66

_______ have lower Hgb and Hct values than men due in part to more tenuous iron stores.

menstruating women

67

what lab measurements are used to define anemia?

Hgb, Hct, RBC count, MCV, MCHC, rDW, WBC count, differentia of various types of WBC (%)

68

what stain is used to observe red cell morphology changes?

Wright’s stain

69

reticulocytes can be identified by presence of _______ in cell for 1st day in circulation.

mRNA. only peripheral cell where you can routinely evaluate production by quantitating # of young cells in circulation. counted as % of 1000 red cells counted.

70

what is the normal % of reticulocytes in the blood?

.4-1.7%. increased is when it’s 3.5-5 fold greater than this.

71

reticulocyte index is useful for correcting reticulocyte counts fro red cell concentration and _________.

stress reticulocytosis. normal RI should be between 1 and 2 for a healthy individual.

72

what are the stress factors for a reticulocyte count?

1.5 (mild anemia>9gm/dl); 2.0 (6.5-9); 2.5 (severe

73

what does and RI >2 with anemia indicate?

loss of RBC leading to increased compensatory production of reticulocytes to replace lost RBC.

74

in anemias that develop over weeks, ________ w/in cells increases to make oxygen dissociation more efficient to compensate for low oxygen carrying capacity.

2,3-DPG. however, if it develops acutely, there is not enough time to make this compensatory mechanism

75

what are some symptoms of anemia?

shortness of breath, fatigue, rapid heart rate, dizziness, claudication, pain with exercise, pallor

76

Know his freaking scheme for anemia

seriously, he’s only shown it to you a million times.

77

is anemia associated with other hematologic abnormalities? YES (means what?)

bone marrow examination to look for: leukemia, aplastic anemia, myelodysplasia, myelofibrosis, myelophthisis, megaloblasitc anemia

78

is anemia associated with other hematologic abnormalities? NO (means what?)

ask next, is there an appropriate reticulocyte response to anemia?

79

is there an appropriate reticulocyte response to anemia? YES (means what?)

is there evidence of hemolysis? (yes or no) increased bilirubin/lactic dehydrogenase, decreased haptoglobin, hemosiderin in urine

80

is there an appropriate reticulocyte response to anemia? NO (means what?)

ask: what are the RBC indices?

81

is there evidence of hemolysis? YES (means what?)

evaluate for cause of hemolysis

82

is there evidence of hemolysis? NO (means what?)

evaluate for hemorrhagic causes of anemia

83

MCV>100

evaluate for macrocytic anemia

84

MCV 80-100

evaluate for normocytic anemia

85

MCV <80

evaluate for microcytic anemia

86

basic concepts of biochemistry/distribution of iron that are important for iron deficiency anemia

1. iron exists in 2 valence states, ferric and ferrous. activity depends on state.; 2. in aqueous solutions Fe forms insoluble hydroxides unless bound to a protein/compound; 3. Fe salts are more soluble than low pH; 4. Fe balance in body is controlled by absorption, there are no active mechanisms for excretion; 5. losses of Fe each day are small (skin/mucosal exfoliation, urine, menstruation)

87

where is the majority of iron contained?

hemoglobin (65%). 6% is in myogolobin, 25% is in ferritin and hemosiderin (storage forms of iron). v. small amount is bound to transferrin. remainder (

88

iron absorption

goes from stomach (pH and gastroferritin optimize solubility)—>duodenum—>brush border of mucosal cell is where dietary non-heme enters—>converted to ferrous iron by DCYTB—> enters cell through divalent transporter—>stored/transported across bask-lateral membrane

89

what increases intraluminal absorption of iron?

presence of protein, vitamin C (for valence state)

90

what decreases absorption of iron?

phytates, oxalates, other food constituents cause it to precipitate and be less biologically available

91

iron cycle

iron is bound to transferrin—>goes to marrow and maturing normoblasts—>transferrin receptors on cells are bound—>normoblast incorporates it into hemoglobin

92

transferrin

84kDa plasma protein made in liver. binds iron in ferric form

93

what happens to iron in dead RBCs?

macrophages turn cells over in spleen, and sequester iron in ferritin stores.

94

what is the ferritin molecule structure?

coat made of 24 alternating H and L chains. center has ferric salts and 4500 atoms of iron can be held in 1 ferritin

95

hepcidin

25 aa peptide mad in liver in response to high iron intake, inflammation, infection.

96

what happens when hepcidin is increased?

plasma flow from stores goes down, iron saturation and plasma iron decrease, erythropoiesis goes down

97

what happens when hepcidin is decreased?

binds to ferroportin, degrades it. iron export out of cell goes down, iron accumulates in ferritin

98

transferrin receptor provides ______ for the iron cycle

direction. transferrin enters cell through clathrin coated pit to make endosomes. become acidified, iron exits endosome through DMT1 to go to storage sites. Transferrin returns to surface

99

what are the general characteristics of iron deficiency?

decreased Hg, decreased cell proliferation, mild hemolytic component (cell rigidity), mildly defective muscle performance, neurophysiological disfunction, nail ridges, upper gastric involvement, immune dysfunction

100

how does iron deficiency develop?

excessive losses, failure to accumulate iron, on-going losses/inability to gain iron during growth

101

steps of iron depletion:

1. iron ferritin levels diminish; 2. iron deficient erythropoiesis; 3. overt anemia

102

how do you diagnose anemia?

start with a history, and look a the various symptoms, look at lab tests

103

differential diagnosis of anemia

anemia of chronic inflammation/infection, anemia of chronic disease, thalassemia, sideroblastic anemias

104

how do you replace iron?

iron salts orally, intramuscular/iv route when absorption altered/compliance is an issue. slowly normalizes, serum iron responds quickly, normal RBCs in 3-5 days.

105

do you stop iron treatment once Hg has reached normal levels?

NO! you need to replenish ferritin stores, so continue for a while after (deficient cells survive 3 months, so need to support)

106

what is iron overload?

increase in body burden of iron beyond the norm. can be caused by increased intake in diet, mutation in HLApH gene, repeated transfusions for anemia.

107

what are the organs damaged by iron overload?

heart, liver, endocrine organs

108

how do you treat iron overload?

therapeutic phlebotomy, chelation (Desferal)

109

each red blood cell contains ______ molecules of Hg.

280 million

110

what is the predominant form of hemoglobin in adults?

A (alpha 2, beta 2)

111

absence of what chain is incompatible with life?

lack of alpha globin chains

112

describe the numbers of amino acids in alpha and beta chains.

141 aa for alpha, 146 aa in beta globin

113

where does heme link to a histadine?

on the 87 on alpha, and the 92 on gamma, beta, s chain

114

how is the delivery of oxygen to tissues accomplished by Hg?

through allosteric regulation. (configuration changes allow different binding affinities)

115

what is a way to quantify the difference in oxygen affinity?

by P50. partial pressure of oxygen where oxygen protein is 50% saturated. P50 for Hg is 27mmHg, myoglobin is 2.75 mmHg

116

basic shape of the O2 dissociation curve mnemonic (pp-%).

30-60, 60-90, 40-75

117

ph of Hg oxygen affinity

affinity increases over pH range of 6-8.5. O2 held more tightly in alkaline situation, easily released when there is a lower pH. Bohr effect

118

hemoglobins oxygen affinity varies ______ with temperature so that at higher temp, more O2 unloaded, less bound by Hg.

inversely

119

2.3-biphosphoglycerate (2,3-BPG)

biproduct of the aerobic glycolytic pathway. present in red cells at concentration of ~5mmol/L

120

chromosome 16 contains the ___ genes, with 2 copies of the _ globin gene itself.

alpha-like, alpha

121

beta like genes and beta globin chain and variants are on chromosome __.

11

122

what are the 3 hemoglobins that are present only btw. weeks 4-14 gestation?

Hemoglobin Gower 1 and 2 and Portland. All have higher affinity O2 than HgA

123

what predominates at 8 weeks gestation?

fetal hemoglobin. Bohr effect increased by 20% in fetal Hg.

124

tell me the ratios of HgF and HgA when a baby is born:

65-95% F, 20% A

125

hemolytic anemia is caused by variants altering _______ affinity.

Hg-O2. unstable molecules are also called Heinz body anemia

126

what are Heinz bodies?

precipitated, denatured Hg.

127

when is erythrocytosis is generally found when?

in people with high affinity hemoglobins b/c O2 delivery to tissues is reduced, causing increased erythropoeitin release from kidneys, stimulating RBC production.

128

Hemoglobin Zurich has a ________ point mutation that doesn’t affect oxygen binding, but does increase CO binding.

single.

129

what results if iron binds Hg when it is in ferric form?

methemoglobinemia. can occur because of too much methemoglbin production or b/c of reduced methemoglobin production

130

how is methemoglobin produced?

oxidation via free radicals, hydrogen peroxide, nitric oxide, OH-. can also occur with drug exposure (anesthetics, nitrates, etc.)

131

what is the most common cause of methemoglobinemia?

hereditary causes, most commonly the homozygous deficiency of cytochrome b5 reductase. also could be a mutation in Hg that causes you to make HgM. causes you to be cyanotic

132

what color is methemoglobinemia blood?

dark red/ chocolate/ blue-brown, doesn’t change with oxygen exposure

133

_______ can be given by IV to provide an artificial electron acceptor for reduction of methemoglobin via NADPH-dependent pathway, giving results in ~1 hour.

methylene blue.

134

when is cyanosis visually perceptible?

when reduced Hg exceeds 3 g/dL, O2 saturation below 85%.

135

how does a pulse oximeter work?

uses photo detectors with 2 light diodes that measure pulsatile flow

136

platelets

clotting factor of the blood. 7-10 days life span in peripheral circulation, 200 billion made per day

137

embryonal stage hematopoiesis

primitive blood cells are produced in yolk sac. finished by month 3

138

fetal stage hematopoiesis

months 2-7 liver and spleen are the sites of hematopoiesis. by birth its established in marrow

139

post natal hematopoiesis

marrow cavity is hematopoietically active. as age progresses, it becomes more localized in axial skeleton. by 18-20 years 90% of marrow is in vertebrae, pelvis, sternum, ribs, skull.

140

extramedullary hematopoeisis

hematopoiesis outside of marrow after birth. very weird and wrong.

141

myeloid

all non-erythroid, non lymphoid cells (eg: granulocytes, monocytes, megakaryocytes, platelets, etc)

142

lymphoid

T, B, NK cells and their precursors

143

self renewal in hematopoiesis

a dividing stem cell can differentiate in the process, so this process produces daughter cells that are unchanged from the original. It does not proliferate but can at a later time

144

mutipotential hematopoeitic stem cell (HSC)

mother of all blood cells, generates lymphoid and myeloid cells. can self renew or become a pluripotent stem cell

145

pluripotential stem cells/colony forming units (CFU)

CFU-GEMM is mother of all non-lymphoid blood cells. CFU-L is the mother of all lymphoid cells. can self renew or become progenitor cells

146

progenitor cells

self renewal is limited, and they commit to differentiating at various lineages.

147

Burst Forming Unit Erythroid (BFU-E)

progenitor cell that becomes CFU-E. comes from the exuberant colonies. can make precursor cells

148

precursor cells

recognizable, maturing cells in marrow specimens. can divide up to a point, but not self-renew. become mature, functional cells in peripheral blood, lymphoid organs, reticuloendothelial system

149

amplification

self renewal. few stem cells can become billions each day

150

bone marrow vasculature

arteries go through the marrow, branching in to capillary-venous sinuses. these are composed of endothelial/basement memb/adventitial layer. these flow into a central vein into systemic circulation. passage of cells into the sinuses is selective-only mature ones can move out.

151

stromal elements play a key role in _________.

hematopoiesis. include endothelial cells of C-V sinuses, reticular cells of the adventitia, fibroblasts, lymphocytes, macrophages, adipocytes, extracellular matrix

152

hematopoietic growth factors (HGF)

man different types exist, work on many target lineages, made by different cell types

153

erythropoietin (epo)

made by kidney cells during hypoxia. promotes erythropoiesis

154

thrombopoietin (tpo)

promotes megakaryopoiesis

155

granulocyte-monocyte colony stimulating factor

GM-CSF. promotes granulopoiesis and monopoiesis

156

granulocyte colony stimulating factor (G-CSF)

promotes granulopoiesis

157

monocyte colony stimulating factor (M-CSF)

promotes monopoiesis

158

interleukin-5 (IL-5)

promotes production of eosinophils

159

interleukin-3 (IL-3)

promotes production of basophils

160

describe steps of erythrocyte maturation

pronormoblast—>basophilic normoblast—>polychromatophilic normoblast—>orthochromatic normoblast—>reticulocyte—>erythrocyte

161

what characterizes erythrocyte maturation?

chromatin condenses and loses parachromatin, the nucleus degrades pyknotsicly, the pyknotic nucleus is extruded and an erythrocyte is formed, hemoglobin is accumulated and the organelles are lost. eventually it can no longer replicate

162

pronormoblast

first erythroid precursor. 18um wide. nucleus has fine, granular chromatin and 1-2 nucleoli. cytoplasm has lots of RNA so it’s very blue

163

basophilic normoblast

cytoplasm is basophilic-but a lighter perinuclear halo can be around. nuclear chromatin is coarser and condensed. smaller- 12-14 um.

164

polychromatophilic normoblast

10-12 um. starting to accumulate Hg. Hg+RNA makes it look purple-blue in cytoplasm. nucleus is smaller with chunky chromatin

165

orthochromatic normoblast

8-10 um. cytoplasm is red-orange from Hg. v. small and shrunken nucleus

166

reticulocyte

anucleate cell, with ribosomes and mitochondria. can be identified after supra vital staining-since it causes mitochondria and ribosomes to condense into strands

167

erythrocyte

reticulocyte ribosomes make Hg for 2-3 days and then they degrade, resulting in a a mature erythrocyte. 7-8um. biconcave disc.

168

list the steps of granulocyte maturation

myeloblast—>promyelocyte—>myelocyte—>metamyelocyte—>band—>segmented granulocyte (seg)

169

what features characterize granulopoeisis?

the nucleus matures with chromosome condensation, the nucleoli are lost, and the nucleus indents to eventually segment. primary and secondary cytoplasmic granules are acquired. eventually the ability to replicate is lost by the metamyelocyte stage

170

myeloblast

15um. 1st precursor. high nuclear:cytoplasmic ratio, fine chromatin, 1 or more nucleoli, blue cytoplasm w/ lots of RNA. no granules

171

promyelocyte

20um. chromatin are condensed/coarse. nucleoli are present. has a variable # of large purple granules. blue cytoplasm

172

myelocyte

15um. lavender secondary granules smaller than primary granules, large golgi, less granules than promyelocyte, condensed nucleus with coarse chromatin. last precursor that can divide

173

metamyelocyte

14-16um. lots of secondary granules that make it look pinkish purple, obscure primary granules (or they may be absent). nuclear chromatin is condensed and coarse and the nucleus has an indent (less than 1/2 the diameter of the nucleus)

174

band

13 um. horseshoe shaped nucleus. lots of secondary granules

175

segmented neutrophil

same size and cytoplasmic properties as band. nucleus is segmented into 2-5 lobes connected by strands

176

eosinophils

13um. cytoplasm is full of large orange-red granules. nucleus has heavily condensed chromatin, segmented into (2) round oval lobes.

177

basophils

10 um. lobular, non-segmented nucleus that is obscured by blue-purple granules.

178

list the steps of megakaryocytic maturation

megakaryoblast—>promegakaryocyte—>megakaryocyte—>platelet

179

what is megakaryocyte maturation characterized by?

dna undergoing repeated doublings (endoreduplication) to form a multilobulated nucleus wi/ around 32 sets of chromosomes. the cytoplasm is filled with granules and a network of membranes allows it to make platelets that it sheds into the vascular sinuses.

180

megakaryoblast

20-30um. large, round/indented nucleus with nucleoli and rim of basophilic cytoplasm. hard to differentiate from other blasts

181

promegakaryocyte

lobulated nucleus with condensed chromatin. granules are in the cytoplasm give an intense blue

182

megakaryocyte

lobulated, endoreduplicated nucleus with lots of cytoplasm that is granular and purpleish

183

platelet

megakaryocyte extends membrane into the lumen of the sinus. chunks break off and float away. 2-4 um, granular, purplish

184

list the steps of monocyte/macrophage development

monoblast—>promonocyte—>monocyte

185

what characterizes monocyte maturation?

nucleus goes from round and indented to variable and irregular. peroxidase-positive lysosomal granules and vacuoles appear in the cytoplasm, and monocytes travel to the connective tissue to become macrophages.

186

monoblast

16um. indented nucleus with fine chromatin and nuclei. blue cytoplasm with no granules.

187

promonocyte

16-18 um. indented nucleus with condensed chromatin and one or more nucleoli. red purple granules are in the cytoplasm

188

monocyte

15-18um, largest in peripheral blood. varied nuclei shape. no nucleoli, cytoplasm is bluish with “ground-glass” appearance. scattered red purple granules

189

cellularity of bone marrow means what?

portion that is hematopoietically active. the non-active part is occupied by stream elements (fat). Decreases with age. should be equal to 100-age

190

myeloid erythroid ratio (M:E ratio)

granulocytic:erythroid precursors, 3:1

191

maturation

precursors should mature, so it should look heterogeneous. lack of maturation is a homogenous apperance

192

marrow should be free of _________ findings.

abnormal. includes things like fibrosis, metazoic tumor, granulomas

193

pathophysiology of anemia of chronic disease

common mechanisms: malignancies/sepsis—TNF decreases Fe stores, decreases EPO, INF-beta inhibits erythropoeisis; chronic infection/inflammation—IL-1 diminishes Fe mobilization/EPO production, INF-gamma inhibits erythroid. Results are related to inability to use irons stores, less EPO, decreased erythropoiesis.

194

what do all anemias of chronic disease have?

reticulocytopenia. characteristically Fe is decreased, TIBC is normal to decreased and ferritin is normal to increased, EPO low

195

lead intoxication anemia

mild/moderate anemia, decreased reticulocyte count, microcytosis, basophilic stippling, increased Zn protoporphyrin. treat with chelation

196

renal insufficiency anemia

not seen until kidney function is

197

thyroid disorder anemia

normochromic, normocytic, microcytosis or macrocytosis. treat with hormone repalcement

198

adrenal insufficiency anemia

normochromic, normocytic

199

_______ and ______ are critical co-factors for normal hematopoiesis.

folic acid and vitamin B1 (cobalamin). the metabolite of folic acid donates a methyl group in the synthesis of methionine from homocysteine cogenerate tetrahydrofolate. this is important in the steps of DNA synthesis.

200

deficiencies in folic acid and vitamin b12 affect the _______ process of RBC precursors in marrow.

maturation. cells will increase in size and arrest in S phase then destroy themselves

201

do plants contribute B12 to the human diet?

NO!

202

where is vitamin B12 released upon ingestion?

in the acidic stomach. IF secreted by parietal cells binds it and then in the terminal ileum it is absorbed and released from IF, binding transcobalamin binding protein 2 (Tc2). It is then transported to the liver for storage or to the marrow for use

203

what is the most common cause of B12 deficiency?

pernicious anemia

204

pernicious anemia

caused by autoimmune destruction of IF producing gastric parietal cells. common in older population.

205

where is dietary folate absorbed?

in the jejunum. It is hydrolized, reduced, methylated before distribution to tissues or liver for storage.

206

what is the most common cause of folate deficiency?

inadequate dietary intake. other causes are malabsorption or increased demand, alcohol consumption.

207

how long does it take to develop folate and B12 deficiencies?

folate is weeks, B12 is months

208

what hematologic changes do you se with megaloblastic anemia?

M:E ratio is altered (more erythroid produced), marrow precursors have large/immature nuclei, anemia is variable in peripheral blood, macrocytosis, retic count is decreased (

209

________ involvement is classic in B12 deficiency

neurologic. sensory abnormalities, loss of proprioception, ataxia, spasticity, gait disturbances, positive babinski reflex may follow

210

if you treat an undiagnosed B12 deficiency with large doses of folic acid, what happens?

the neurologic damage can be exacerbated

211

what tests show B12 and folate deficiencies?

cobalmin (but must be aware won’t show deficiencies in tissues), serum folate, red folate, plasma homocysteine levels (more sensitive), methylmalonic acid levels

212

once B12 deficiency is diagnosed, it is important to know the ______.

cause.

213

shilling test

1ug of cobalamin given orally, IF combines with it and it eventuallyy enters bloodstream. Flushing dose give via IM at 2 hours to saturate trancobalamins. 5-35% of the absorbed Cbl is exceed in 24 hours due to being “wahshed out”

214

how do you treat B12 and folate deficiencies?

inject/oral B12. 1mg/day of oral Folate or parenterally.

215

thalassemia is a condition where there is ______ of a hemoglobin chain due to a variety of mutations that result in _____ or _____ function of the globin gene.

underproduction, poor or absent

216

alpha thalassemia

alpha chain is underproduced due to absence of 1 or more of 4 genes that control production. common Asian, African Mediterranean descent

217

beta thalassemia

beta globin chain is underproduced, due to point mutations resulting in dysfunctional genes. HbE is structurally abnormal hemoglobin due to point mutation (unstable), lower in RBC due to the instability causing changes. mediterranean, african, SE asian descent.

218

list the consequences of thalassemia defects:

low concentration of Hg in RBC, imbalance in chain production, increase in other hemoglobins

219

RBCs in thalassemia and HgE are ______, and have ______ MCHC with an excess of membrane, giving them a “target cell” shape.

smaller (low MCV), lower

220

underproduction of one globin chain results in ________ of the other globin chain.

unmatched excess. unused chains can precipitate, denature and oxidize, damage cell membranes and make RBCs more fragile.

221

diagnosis of Beta thalassemia is based on recognition of ___ and ____ relative to underproduced HbA1.

HbA2, HbF

222

if a person with Beta thalassemia becomes iron deficient, are you more or less likely to catch their thalassemia?

less. HbA2 values will appear normal instead of high due to the iron deficiency. you must be sure they aren’t iron deficient before starting Hg electrophoresis to evaluate for thalassemia

223

anemia with some increase in reticulocyte count in relation to chronic hemolytic anemia

degree will vary with thalassemia severity. Cooley’s anemia needs regular transfusions to sustain life. others may not need transfusions till later/or at all

224

chronic hemolytic anemia has:

anemia with increase in reticulocyte count, abnormal peripheral smear, splenomegaly, abnormal chemistry profile

225

how does bone marrow attempt to produce adequate RBC mass with thalassemia?

bone marrow expands to fill with RBC precursors even though they are ultimately fragile and destroyed.

226

people with severe forms of thalassemia ______ absorption of iron from the diet in response to anemia.

increase.

227

anemia, increased metabolism and ineffective erythropoiesis and encocrinopathies contribute to ______ growth and development.

delayed. can result in short stature and delayed puberty.

228

nearly 2/3 of patients with ________ anemia have abnormal endocrine function

Cooley’s. pituitary is affected, hypothyroidism/impaired glucose may occur (40-60% of patients)

229

persons with chronic hemolytic anemia (inc. thalassemia) are at risk for __________.

pulmonary hypertension. more common in splenectomy patients

230

how do you treat thalassemias?

transfusion support (combined often with chelation therapy and splenectomy), increasing fetal hemoglobin production, and bone marrow transplantation.

231

sickle cell is:

a. autosomal recessive

b. both B-globin genes are mutated

c. there is a single amino acid substitution

D. heterozygosity provides carrier advantage e. all of the above are true

All are true!

232

sickle cell disease occurs in people with 2 abnormal __________ genes where at least one of these has the sickle mutation.

beta globin. if the other gene also has the sickle cell mutation the disease is sickle cell anemia (HbSS)

233

sickle cell trait

occurs in person with 1 sickle cell gene and 1 normal gene. protects against disease devleopment

234

when deoxygenated, sickle hemoglobin polymerizes into _____strand helical fibers that ______ the shape of the RBC into a sickle form or other irregular shape

14; distort

235

when does a cell become irreversibly sickled

after several deoxygenation-reoxygenation cycles

236

the shape of the sickle RBC results in chronic hemolytic anemia-describe the characteristic changes in lab tests seen with this

anemia with compensatory increase in reticulocyte count, increased baseline WBC and platelet count, increased RDW, abnormal peripheral smears (sickle forms, schistocytes/broken cells, polychromasia/blue colored cells, anisocytosis/variation in size, poikilocytosis/variation in shape), abnormal chemistry profile

237

howell jolly bodies

small purple dots in RBCs. seen in patients w/o functioning spleen

238

target cells and hemoglobin C crystals

red “rods” in RBC, seen in HgSC

239

microcytosis

low MCV and target cells in SBthalassemia (+/- versions)

240

what shows up in an abnormal chemistry profile with SCD?

increased total/indirect bilirubin, lactate dehydrogenase (LDH) and aspartate aminotransferase as RBCs are lysed

241

what are the implications of chronic hemolytic anemia (SCD)?

aplastic crisis, growth retardation/delay, bilirubin gallstones

242

aplastic crisis

anything compromising bone marrow ability to produce RBCs can drop Hg quickly. Found via low reticulocyte count. can result from Parvos virus, infection, medication, vitamin deficiencies

243

RBCs in SCD are “_____” due to membrane injury and retention of adhesion molecules on surface.

Sticky!!! this results in adhesion of sickled RBCs in microvascular circulation. results in vaso-occlusion, vessel wall injury, endothelial remodeling, vessel narrowing, chronic organ damage

244

what organs are most affected by chronic RBC adhesion/vascular occlusion

spleen, CNS, lung, kidney, retina, femoral/humeral heads

245

spleen damage in Chronic RBC adhesion/vascular occlusion

large numbers of RBC trapped—>severe anemia and circulatory show occurs; splenic sequestration. results in autoinfarction/destruction of seen by 5 y/o.

246

CNS damage in Chronic RBC adhesion/vascular occlusion

up to 10% of children with HbSS have overt large vessel stroke due to chronic injury. learning disabilities and neurologic problems can occur. can be reduced w/blood transfusions.

247

lung damage in Chronic RBC adhesion/vascular occlusion

damage to microvessels makes it hard to let blood flow through, resulting in high pressure in pulmonary arteries—pulmonary arterial hypertension. puts strain on R side of the heart

248

kidney damage in Chronic RBC adhesion/vascular occlusion

tubules damaged via chronic vaso-occlusion. cannot concentrate urine to avoid dehydration. may have papillary necrosis (ischemia of collecting system) leading to blood in urine. renal insufficiency and permanent scarring/damage of glomerulus common

249

retina damage in Chronic RBC adhesion/vascular occlusion

vessels can form abnormally in retina and hemorrhage, leading to detached retina and blindness.

250

other issues and damage in Chronic RBC adhesion/vascular occlusion

femoral/humeral head avascular necrosis, joint deterioration, hip/shoulder replacement. skin ulcers, poor healing

251

sickle cell crisis

hypoxia, dehydration, inflammation, infection and stressors lead RBCs to sickle and leads to blood vessel damage and constriction—sudden vaso-occlusion. causes severe pain (commonly in arms, legs, chest abdomen).

252

what are other significant acute faso-occlusive complications?

hand-foot syndrome (swelling), acute chest syndrome (fluid leaks into lungs), acute multi-organ failure syndrome (renal and liver failure), priapism (ouchie), bone infaction (focal areas sustain ischemia, damaged, necrotic, painful)

253

list the 3 main treatments of SCD:

bone marrow transplantation, hydroxyurea therapy (chemo agent that induces fetal hemoglobin), transfusion therapy

254

how long do people with SCD live typically?

into their 50/60’s if cared for properly

255

hemolysis

decrease in RBC survival or increase in turnover beyond standard norms. determines whether anemia presents acutely or chronically.

256

what are the 2 mechanisms for red cell destruction to exist?

turnover w/in vascular space (intravascular) and ingestion/clearance by macrophages of the reticuloendothelial system (RE) (extravascular)

257

red cells undergoing intravascular hemolysis release Hg into __________.

circulation. tetramer form of Hg dissociates and binds haptoglobin, which is removed by the liver. Fe can also be oxidized to form methemeoglobin, dissociation of globulin means methane can bind albumin/hemopexin, both of which can be taken up by parenchymal cells and made into bilirubin.

258

in extravascular hemolysis, red cell is ____ by ____ of RE system.

ingested, macrophages. heme is separated from globin, iron is stored in ferretin, porphyrin ring is made into bilirubin. bilirubin is made water soluble by glucuronic acid via cytochrome P-450 enzyme in liver. It is then converted to urobilinogen which cycles in gut/liver or is excreted.

259

_______ is _______ if hemolysis is brisk enough o overcome bilirubin processing of liver, leading to increase in unconjugated fraction.

bilirubin, increased

260

what else suggests an increase of intravascular hemolysis?

decrease in serum haptoglobin levels, hemoglobin in urine or plasma, increase in methane or methealbumin

261

hereditary spherocytosis (HS)

familial disorder: anemia, intermittent jaundice, spenomegaly (responds to spelnectomy). loss of plasma membrane and formation of microspherocyte (suceptible to osmotic stress). Spectrin/ankyrin/band 3 weaken cytoskeleton to destabilize lipid layer. this leads to entrapment in spleen. Mostly auto dom, 25% is auto recessive. treat for chronic anemia, splenectomy. can result in aplastic crises and bilirubin stones.

262

glucose 6 phosphate dehydrogenase (G-6-PD) deficiency

sex linked recessive. may help with resistance to plasmodium vivid. G-6-PD provides protection against oxidant stress. loss of enzyme early on=denatured Hg attaches to membrane and damages spectrum. resulting deformability means splenic trapping and extravascular hemolysis.

263

Pyruvate Kinase (PK) deficiency

second most common enzyme deficiency, most common glycolytic defect. decreases conversion of phosphoenolpyruvate—>pyruvate, results in less ATP. Membrane plasticity down, destruction in spleen. support with folate, transfusion, supportive care

264

autoimmune hemolytic anemia

antibodies to universal red cell antigens can cause hemolysis bi intra/extra vascular destruction. Cold and hot.

265

cold antibodies

IgG/M bind red cell membrane in cooler areas of body, when they move back into the body they activate complement through C5-9 attack complex, makes holes in membrane. It dissociates at higher temperature and the cell destructs.

266

warm antibodies

IgG. bind cell with big affinity. have no/poor complement activating capacity, incites splenic macrophage to do antibody-mediated phagocytosis through Fc receptor. results in extravascular hemolysis

267

what tests are used for autoimmune hemolytic anemia?

antiglobulin or Coombs tests for IgG and or complement on cell surfaces. warm=positive DaT, max reaction at 37C, panagglutining w/o antigen specificity. cool=positive DAT, max react at 4C,antigen specifically for I or i

268

the most significant complication of splenectomy is ____ _____ _____, particularly associated with S. pneumonia. This risk is greatest in children

overwhelming bacterial sepsis

269

what temp is a trigger that you need to see your doctor if you have had a spenectomy?

>38.5C. see immediately for febrile illness

270

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orthochromic normoblast

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270

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Pronormoblast

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271

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basophilic normoblast

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272

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polychromatophilic normoblast

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273

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reticulocyte

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274

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megakaryocyte

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myeloblast

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276

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promyelocyte

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myelocyte

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278

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metamyelocyte

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279

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band

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280

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segmented neutrophil

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281

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eosinophils

282

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basophils

283

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mast cells

284

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monoblast

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285

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promonocyte

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monocyte

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lymphoblast

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lymphocyte

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289

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290

the freaking chart we have to know

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291

hemoglobin and myoglobin binding curves

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292

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heinz bodies

293

alpha thalassemia table

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294

beta thalassemia table

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295

CBC thalassemia lab results

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296

sickle cell disease table

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297

Development of Iron deficiency Table

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Newborn Screening Tests table

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