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Flashcards in Hematology Deck (110)
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1

Leukemia vs. Lymphoma

Leukemia: malignancy in the marrow
Lymphoma: malignancy outside of the marrow, usually WBCs in a secondary lymph organ

2

Acute vs. Chronic Leukemia

Acute involves immature cells, more rapid
Chronic involves more mature cells

3

Measured components of CBC (8)

WBC, RBC, Hemoglobin, Hematocrit, Platelet Count, Mean Corpuscular Volume, Differential, Mean Platelet Volume

4

Calculated Components (6)

Hematocrit, Mean Corpuscular Volume, Mean Corpuscular Hemoglobin, Mean Corpuscular Hemoglobin Concentration, Red Cell Distribution Width, Absolute Leukocyte Counts

5

Transcription Factor most common in innate immunity

NFk-B

6

Cytokine vs. Chemokine

Cytokine: general small protein signaling molecule
Chemokine: cytokine that promotes chemotaxis

7

Purpose of innate immune system

Start inflammation quickly, Rubor/Calor/Tumor/Dolar
Signals adaptive immune system through dendritic cells

8

Reticulocyte Count
Absolute Reticulocyte
Reticulocyte Index

Count: counting on slide, 0.4-1.7% of total cells
Absolute: Percentage x RBCs. >50,000/uL is elevated
Index: fold increase beyond baseline, countx(pt/normHgb)x1/stress factor, 1-2 is normal

9

Anemia General Symptoms and Signs

Symptoms: SOB, Tachy, dizziness, fatigue, claudication, angina, pallor
Signs: tachycardia, tachypnea, dyspnea, pallor

10

Iron Distribution

65% Hemoglobin, 6% myoglobin, 25% ferritin/hemosiderin,

11

Iron Absorption

Iron from food made soluble in gastric pH

Gastroferrin binds elemental or heme-bound iron

Ferric iron is transported into cells through DMT1 transporter and DCYTB converts ferric (3+) iron to ferrous (2+) iron.
Either bound to ferritin in cell or exported via ferroportin and converted to ferric through hephaestin

Hepicidin inhibits ferroportin. AAs and VitC improve absorption. Erythropoiesis improves absorption.

12

Iron Transport

Transferrin binds 2 moles ferric iron and delivers to bone marrow. Interacts w/ transferrin R, clathrin-mediated pinocytosis.
pH in endosome causes iron dissociation and it enters cytoplasm through DMT1.

13

Development of Iron Deficiency

See reduced Hemoglobin, RBC production, cell rigidity.
Causes: failure to absorb or inability to keep up w/ production demands.
1. Iron depletion in ferritin stores, absorption increases, functions are normal
2. Serum iron reduced, iron binding affinity increases, iron loading is impaired, normal RBC production.
3. Low serum iron, increased transferrin, reduced erythropoiesis,
Signs: microcytosis, hypochromia, increased protoporphyrin

14

Symptoms of Iron Deficiency

Pallor, Fatigue, Loss of Exercise Tolerance, Irritability,

15

Effects of Iron Deficiency

Heart, Liver, Endocrine disorders

16

Treatments of iron deficiency

Phlebotomy, Chelators

17

Hemoglobin only binds __ Iron

Ferrous (2+)

18

P50 Oxygen in body

27mmHg

19

pH and oxygen affinity

decreases as pH decreases

20

[CO2] and oxygen affinity

decreases as CO2 increases

21

Temperature and oxygen affinity

decreases as temperature increases

22

2-3BPG

Binds between beta chains, stabilizes T conformation.
Affinity decreases as enzyme increases

23

Myoglobin vs. Hemoglobin oxygen dissociation curves

Myoglobin is monomer, no cooperativity, hyperbolic dissociation curve hyperbolic w/ high affinity at low concentration.
Poor O2 transporter b/c dissociation only occurs at very low O2 but effective in very low O2 environment of cell.

24

Hemoglobin 4-14 weeks

Z2E2 and A2E2

25

Hemoglobin 18 weeks - Birth

A2G2

26

1-5 Years onward

A2B2 and little A2D2 (2%)

27

Hgb Chesapeake

Increased affinity, red appearance, high RBC count

28

Hgb Zurich

Increases CO2 affinity, similar to smokers

29

Hgb Koln

mild anemia, reticulocytosis, splenomegaly

30

Methemoglobin

Hemoglobin binding ferric iron, usually 1%
Caused by NADPH metHgb reductase deficiency or increased free radical exposure.
Genetically: cytochrome b5 reductase deficiency

31

CO affinity for Hgb

250x higher, smokers 10-15% (normal 3%). Negative cooperativity

32

How does a pulse oximeter work?

DeoxyHgb absorbs 660nm; OxyHgb absorbs 940nm. Only pulsatile flow measured. CO heme absorbs 940, MetHgb absorbs both

33

Where does hepatopoiesis occur?
0-3 months, 2-7 months, 7-9 months, Childhood, Adult

0-3 months Yolk Sac
2-7 months Liver w/ some spleen
7-9 months Bone Marrow
Childhood Most BM
Adult Axial BM

34

HSCs and Progeitor Cells

HSCs self renew and become colony stimulating units
Progenitors: limited self renewal, limited to 1-2 lineages w/in set
Precursors: dedicated to 1 lineage

35

Major Growth Factors

EPO
Throbopoietin
Granulocyte-Monocyte/Granulocyte/Monocyte CSFs
IL-5 (Eosinophils)
IL-3 (Basophils)

36

Blast Cell

large nucleus, immature cytoplasm (blue), large nucleolus

37

Erythropoiesis Timeframe

2-7 days maturation in BM w/ 3-5 days of division.
Reticulocytes 1 day BM and 2-3 days in periphery
120 day lifespan

38

Granulopoiesis

3-5 days mitotic pool
5-7 day maturation
10 hour lifespan

39

Things to evaluate w/ marrow biopsy (6)

Cellularity (100-age)
Myeloid-Erythroid ratio: 3:1
Maturation: heterogenous appearance
Reasonable # of megakaryocytes
Proper iron amount in macrophages (Prussian Blue)
Lesions: no fibrosis, tumors, granulomas, etc.

40

Normal WBC results

4,500-10,500 WBCs/uL
40-60% neutraphils, 1-4% eosinophils, 0.5-1% basophils, 2-8% monocytes, 20-40% lymphocytes

41

Major Central Lymphoid Organs

Bone Marrow and Thymus

42

Peripheral Lymphoid Organs

Lymph Nodes, Spleen, Peyer Patches, Tonsils

43

Blood-Lymph Circulation of Lymphocytes

Extravasate in post-capillary venules at high cuboidal endothelial cells. Either stay in lymph node or enter lymph and return to system circulation via at SVC.

44

Immunogen

Antigen that elicits an immune response after binding an AB/TLR
High affinity, multiple bound ABs, co-stimulation of other surface molecules important

45

Anemia of Chronic Disease Causes (4)

Neoplasms and Sepsis
Chronic Inflammation/Infection
Renal Issues
Lead

46

Anemia of Chronic Disease Pathogenesis

TNF from neoplasms/sepsis reduces erythropoiesis, iron stores, and INF-beta which collectively reduce erythropoiesis.
Inflammation/Infection produces IL-1 which reduces erythropoietin and iron metabolism. Also produces INF-gamma which suppresses erythropoiesis.
Renal is lack of erythropoiesis
Lead inhibits protoporphyrin ring synthesis and iron addition to rings

47

EPO vs. Transfusion treatments for chronic anemia

EPO preferred for absolute deficiencies or EPO loss.
Transfusions indicated when heart damage possible.

48

B-12 and Folate Deficiencies (basis)

Both important co-factors for hematopoiesis, covert methionine to homocysteine which creates tetrahydrofolate for DNA synthesis. Decreases cause RBCs to decrease in size, arrest in size, and get destroyed.

49

B12 sources/absorption

Meat, Eggs, Milk. It is released in acidic gastric environment and binds Intrinsic Factor from GI cells, absorbed in terminal ileum and released from IF, binds transcobalamin binding protein II that transports it to liver for storage or bone marrow for use.

50

Folate sources/absorption

Folate is in many foods, absorbed in jejunum, hydrolyzed, reduced, and methylated before distribution to tissue or stored in liver. Biliary secretion and enterohepatic circulation provides constant supply for tissue.

51

Bone Marrow Findings in B12/Folate Deficiency

Erythroid hyperplasia. Megaloblastic changes. Larger nuclei than anticipated based on maturity level.

52

Peripheral Blood Findings B12/Folate Deficiency

variable anemia, low reticulocyte count, macrocytosis, high bilirubin, and high LDH.

53

Causes of B12 anemia (3)

Autoimmune destruction of IF producing epithelial cells
Lack of IF synthesis
Malabsorption of B12

54

B12 deficiency timeline

Slow. High liver stores take long time to deplete w/ long half life for b12. Neruoabnormalities possible.

55

Causes of Folate Anemia (2)

Inadequate Dietary intake
Malabsorption (enterohepatic circulation disruption, alcohol consumption)

56

Folate Deficiency Timeline

Much faster than B12. Neuro abnormalities rare.

57

Diagnosing B12/Folate Deficiency

Both produce elevated plasma homocysteine. B12 also produces high methylmalonic acid levels.

58

Treatments for B12/Folate

Cobalamin deficiency treated w/ IM or SC daily for 2 weeks with monthly doses for life.
If absorption is not an issue, can be given PO
Folate given orally or parenternally

59

Hemoglobin tetramers through development

0-4 Months: A2E2 and Z2E2
4-Birth: Fetal A2G2
After birth: A2B2 w/ 2% A2D2

60

Alpha Thalassemia usually caused by.....

Deletion on Chromosome 16

61

Beta Thalassemia usually caused by....

Point mutation on Chromosome 11

62

Clinical Signs of Thalassemia

Low Hgb, Low MCV, Low MCHC,

63

Alpha Thalassemia Trait

Silent: 1/4 deleted genes, no anemia, normal MCV
Trait: 2/4 deleted, no/mild anemia, normal/low MCV
NO transfusions needed

64

HgH Disease

3/4 alpha genes deleted, mod/severe anemia, low MCV, transfusions sometimes needed

65

Hydrops Fetalis

4/4 alpha genes deleted, incompatible with life

66

Thalassemia Smear Findings

microcytosis, target cells, polychromastia, normal RDW

67

Clinical manifestations of thalassemia

High bilirubin, AST, LDH from hemolysis, splenomegaly, expanded bone marrow, increased iron absorption, delayed growth, pulmonary HTN

68

Iron Valence States

Ferric 3+ and Ferrous 2+

69

Iron in Aquesous Solution Considerations

Forms insoluble salts unless protein bound

70

Where are Iron salts more soluble?

Low pH

71

How is body Iron balance controlled?

Absorption, no mechanism for excretion

72

How do you lose body iron?

exfoliation of skin/musosa, menstruation

73

Hemoglobin: 30-60; 60-90; 45-75; 10-10

Pneumonic for pO2 and % binding

74

Lifespans and daily production (RBCs, platelets, Neutrophils)

RBCs: 120 days; 175 bil/day
Platelets: 7-10 days; 200bil/day
Neutrophils: 7 hours; 70 bil/day

75

Hemoglobin E

Beta globin gene PM: 26 glu-lys. Unstable. Low MCHC

76

Hydroxyurea in Beta Thalassemia

Induces production of gamma chains, increases HbF

77

HgC Mutation

Beta6 Glu-Lys

78

HbD Punjab Mutation

Beta121 Glu-Gln

79

HbE Mutation

Beta26 Glu-Lys

80

HbO Arab Mutation

B121 Glu-Lys

81

HbS Mutation

Beta6 Glu-Val

82

Sickle Cell HbSS RBC Lifespan

20 days

83

Complications of chronic hemolytic anemia (4)

Aplastic Crises (Parvovirus B19)
Growth delay
Biliruibin Gallstones
Vascular Occlusion

84

Effects of Vascular Occlusion in hemolytic anemia (8)

Spleen: sequestration and auto-infarction
CNS: large vessel occlusion stroke when young hemorrhagic stroke when older from damage
Lung: occlusion and damage, pulmonary HTN
Kidney: dehydration 2' to damage, glomerulus damage
Retina: detachment and blindness from hemorrhage
Avascular necrosis in joints
Skin ulcers

85

Sickle Cell Pain Crisis

Vaso-occlusion and temporary ischemia causing pain in the extremities, abdomen, chest

86

Complications w/ pain crises (vaso-occlusion) (5)

Hand-Foot Syndrome
Acute Chest Syndrome (deoxygenation, pulmonary edema)
Multi-organ failure syndrome
Priapsim (sustained painful erections 2' to trapped RBCs)
Bone Infarction: necrotic injury

87

Treatments of Sickle Cell (3)

Bone Marrow Transplant: Curative
Hydroxyurea: fetal hemoglobin production
Transfusion Therapy: for severe acute circumstances

88

Hereditary Spherocytosis Cause

Defect in spectrin ankyrin, or band 3 that weakens cytoskeleton and destabilizes lipid bilayer. Decreased deformability leads to entrapment in spleen and extravascular hemolysis via macrophages.

89

G-6-PD deficiency inheritance

Sex-linked Recessive

90

G-6-PD Pathology

Loss of G-6-PD creates inability to restore reduced GSH, increased oxidative damage to spectrin, reduced deformity, splenic trapping, macrophage hemolysis

91

Warm AB Autoimmune Hemolytic Anemia

IgG bind RBCs in warm areas of body, poor complement activation, Fc Receptor mediated macrophage hemolysis in spleen

92

Cold AB Autoimmune Hemolytic Anemia

IgG/IgM bind RBCs in cold ares of body, activate complement for intravascular hemolysis

93

Direct DAT/Coombs test

Tests for IgG/C3d/C4d on patient's RBCs by adding ABs against these components and testing agglutination

94

Indirect DAT/Coombs

Checks if patient's serum has IgG/complement that binds normal RBCs

95

Spleen Immunity Function

Creation of IgM, especially for encapsulated organisms

96

Complications of Splenectomy

Bacterial sepsis from S pneumoniae

97

Co-treatments w/ splenectomy

H influenza b, S pneumoniae vaccinations, and meningococcus vaccinations. Prophylactic ABX daily through childhood. See physician immediately w/ F

98

IgG Half Life

3 weeks

99

C1 Esterase Inhibitor

Suppresses basal complement activation from minimal concentration AG activation. Makes C1 unable to activate C4 and lead to cascade.

100

T Helper 1

Release lymphokines to attract macrophages

101

T Helper 17

Similar to TH1s but more powerful

102

T Helper 2

Stimulate macrophages to wall-off pathogens and start healing process

103

Follicular Helper T

After activation, move to B cell region of lymph node to promote B cell activation and class switching

104

Regulatory T Cell

Suppress activation/function of T helpers to stop immune response

105

Type I Immunopathology

Too much IgE, hypersensitivty

106

Type II Immunopathology

Antibodies that react to self or collateral damage to self from AG binding cells

107

Type III Immunopathology

Antibodies to soluble antigens, cause local damage through complement activation

108

Type IV Immunopathology

T-cell mediated damage to self (hepatitis, TB)

109

How many constant heavy chain segments in each type of AB?

3 for IgG, IgD, IgA
4 for IgM and IgE

110

Unique physical characteristics of AB types

IgD: big hinge region
IgM: pentamer, 1 J chain
IgE: lots of sugars associated
IgA: secretory component, 1 J chain