Basics of Hematology Flashcards
1
Q
Hematopoiesis
A
Formation of blood cellular components
2
Q
Erythropoiesis
A
Process by which RBCs are produced
3
Q
Hemostasis
A
The arrest of stopping of bleeding
4
Q
Thrombosis
A
Formation of a blood clot inside a blood vessel that obstructs the flow of blood
5
Q
What are the 5 types of WBCs in blood?
A
Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils
6
Q
Platelets (what, where, how)
A
Small cell fragments produced from MEGAKARYOCYTES found in the bone marrow. Reponsible for hemostatis, which results from interaction between platelets, endothelium, and blood coagulation factors
7
Q
Hematocrit
A
RBC/Total
Expressed as a percentage
8
Q
What is plasma composed of?
A
Proteins, Lipids, Salts, Carbohydrates
9
Q
What is the Buffy Coat?
A
Composed of WBCs and Platelets. Between RBC (bottom) and Plasma (top) when a vile of blood is spun down
10
Q
RBC metabolism
A
No mitochrondria, so dependent of anaerobic metabolism. Reduction through glutathione pathway. Dependent on NADPH through pentose phosphate shunt
11
Q
Hemolysis
A
RBC destruction
12
Q
Normal RBC morphology
A
Circular, biconcave disc-shaped. Mean size 7.5um. Lacks nuclei. Eosinophilic cytoplasm. Central area of pallor, less that 1/3 the diameter of the cell
13
Q
Causes of Abnormal RBC Count
A
Anemia: Decreased RBC due to blood loss, destruction, or insufficient erythropoiesis
Erythrocytosis/Polycythemia: Increased RBC due to reactive changes (smoking), thalassemia, or primary marrow neoplasm
14
Q
Causes of Abnormal Hemoglobin Concentraion
A
Anemia: Decreased due to blood loss, destruction, or insufficient erythropoiesis
Erythrocytosis/Polycythemia: Increased RBC due to reactive changes (smoking), thalassemia, or primary marrow neoplasm
15
Q
Causes of Abnormal Hematocrit
A
Decreased due to anemia of fluid overload
Increased due to erythrocytosis/polycyhemia or dehydration
16
Q
Mean Corpuscular Volume (MCV)
A
Mean size of RBC
17
Q
Causes of Abnormal MCV values
A
Low for Microcytosis, iron deficiency anemia or thalassemia
High for Macrocytosis, megaloblastic anemia
18
Q
Mean Cell Hemoglobin (MCH)
A
Mean quantity of hemoglobin in a single red cell
parallels MCV. If MCV goes up or down, MCH goes up or down
19
Q
Causes of Abnormal MCH values
A
Low MCH: Hypochromatic, iron deficiency anemia
High MCH: Hyperchromatic, megaloblastic anemia
20
Q
Red Cell Distribution Width (RDW)
A
Measure of the variability in size of red cells. The wider the cell histogram, the higher the RDW.
21
Q
Causes of Abnormal RDW values
A
Increased in anemia and disease with RBC destruction (ie schistocytosis)
22
Q
Neutrophil
A
A granular WBC. The most common type of WBC. Primary role in inflammation and destroy pathogens via phagocytosis
23
Q
Neutropenia
A
Decreased absolute neutrophil count
24
Q
Causes of Neutropenia
A
Infections, Drugs, Ionizing radiation, Marrow diseases, Bone marrow infiltration by tumors, Autoimmune disease, Congenital neutropenia
25
Neutrophilia
Increased in absolute neutrophil count
26
Causes of Neutrophilia
Physiologic (neonates, exercise, emotion, pregnancy, lactation), Acute inflammation (infections, surgery, infarcts, autoimmune), Malignancies, Drugs (adrenaline, corticosteroids, lithium)
27
Eosinophil
A WBC with lobed nucleus and cytoplasmic granules. Contribute tot he destruction of parasites and to allergic reactions by releasing chemical mediators (ie histamine)
28
Eosinopenia (and causes)
Decrease in eosinophils. Caused by drugs (corticotrapin, corticosteroids, epinephrine, histamine) or Acute inflammation or Infection
29
Eosinophilia (and causes)
Increase in eosinophils. Caused by: Infections (parasites or fungi), Allergic disorders, Leukemias, Churg-Strauss syndrome, Malignancies
30
Basophil
One type of granulocytic WBC. Essential to the innate immune response of inflammation because they release histamine. Usually two nuclear lobes
31
Basopenia (and causes)
Decreased Basophil count. Caused by Acute Hypersensitivity reactions, Autoimmune, Cushings Syndrome, Pregnancy, Drugs (progesterone, corticosteroids, corticotrophin)
32
Basophila (and causes)
Increased basophil count. Caused by Mastocytosis, CML, basophilic Leukemia, Eosinophilic Leukemia, pH-positive acute Leukemia
33
Monocyte
Mononuclear, phagocytic WBC. Derived from myeloid stem cells. They circulate the blood for 24 hours and then move to tissues where they mature into macrophages
34
Monocytopenia (and causes)
Decreased monoctye count. Caused by aplastic anemia, Cyclic neutropenia, Hemodialysis, Severe Thermal Injuries AIDS, Hairy cell Leukemia
35
Monocytosis (and causes)
Increased monocyte count. Caused by Marrow diseases, Hodgkin's disease, Carcinoma, Multiple Myeloma, Being an Infant
36
Lymphocyte
WBC, mostly found in lymph nodes and spleen. Mostly small, but can be large if reactive. Condensed chromatin.
37
Lymphopenia (and causes)
Decreased Lymphocyte count. Caused by DiGeorge syndrome, Severe combined Immunodeficiency, HIV, malaria, TB, Cushings Syndrome, Hodgkins disease
38
Lymphocytosis (and causes)
Increased Lymphocyte count. Caused by certain viral infections (EBV, CMC, primary HIV infection, Chickenpox, Smallpox, MMR). Occurs naturally in infants and young children. Also occurs after a splenectomy
39
Thrombocytopenia (and causes)
Decreased platelet count. Caused by Peripheral destruction, Sequestration of spleen, Inadequate production
40
Thrombocytosis (and causes)
Increased platelet count. Caused by Primary marrow neoplasm, inflammation, surgery, splenectomy, iron deficiency anemia, hemorrhage
41
Morphology and Parameters of Iron Deficiency Anemia
Small RBC, Larger central pale area, Target cells.
Increase in RDW
Decrease RBC, HGB, HCT, MCV, MCH, MCHC
42
Spheroctyes
Abnormal RBC
| Spherical, No central pallor. Due to decreased cell membrane. Increase MCHC
43
Bite cells
Abnormal RBC
| Bite-like defect due to removal of Heinz body in spleen. Associated with G6PD deficiency
44
Schistocytes
Abnormal RBC
Fragmented RBC, helmet cells
Seen in burns, mechanical heart cells
45
Target cells
Abnormal RBC
Central hemoglobin, target shape.
Seen in Thalassemia, Hemoglobin C, Iron deficiency, Liver disease
46
Basophilic Stippling
Morphology of evenly dispersed find blue granules that are composed of aggregated ribosomes (rRNA). Caused by lead poisoning, thalassemia, sideroblastic anemia, or Infection
47
Howell-Jolly Bodies
Morphology of a single, dense, blue dot containing nuclear DNA remnant. Caused by splenectomy, Fungal, Megaloblastic anemia
48
Heinz Body
Denatured/oxidized hemoglobin attached to inner cell membrane. Stained with supravital dye. Caused by G6PD deficiency and associated with Bite Cells
49
Dohle Body
Abnormal WBC inclusion
Pale blue inclusion at the periphery of cytoplasm, contains condensed RNA. Caused by Infection, Inflammation, Burns or Pregnancy
50
Toxic Granulation (Hypergranularity)
Increase in numbers and prominence of 10 granules. Due to rapid cell division. Often associated with Dohle Bodies. Caused by bacterial infection or marrow recovery
51
Hypersegmented Neutrophils
More than 5 nuclear lobes. Associated with Megaloblastic Anemia
52
What is the Wright-Giemsa Stain
Used to stain peripheral blood smear. Basic elements are orange-red (hemoglobin, basic proteins and some cytoplasmic granules). Acidic elements are stained purple-blue (DNA, RNA, Basophil granules, Cytoplasm of mature Lymphoctyes and Monocytes)
53
What are the types of WBC are normally found in peripheral blood
Lymphocytes (T-cells, B-cells, NK cells)
Granulocytes (neutrophils, eosinophils, basophils)
Monocytes
54
What WBC types fluctuate with age?
Neutrophils, Monocytes, Lymphocytes (most abundant WBC in childrent up to 8)
55
Reticulocytes
Young, anucleated RBCs that retain some RNA, ribosomes and other organelles that enable ongoing production of hemoglobin. Retained in marrow for 3-4 days, then circulate for 1-2 days before maturing
56
Where does hematopoiesis occur throughout life?
Fetal- Yolksac until 3months gestation, then Liver/spleen
Birth- Bone marrow
Child- localized to axial skeleton
Adult- vertebrae, pelvis, sternum, ribs, skull
57
What does Myeloid mean?
Pertaining to, derived from, or resembling bone marrow
| ie Granulocytes, RBC, Platelets, Monocytes, Lymphocytes
58
The progression of a Stem Cell
Stem Cell >> Progenitor >> Precursor >> Mature Cell
59
What are the Hematopoietic Growth Factors (HGFs)
Erythropoietin (Epo)
Interleukin-3 (IL-3)
Granulocyte colony-stimulating factor (G-CSF)
Granuloctye-macrophage colony-stimulating factor (GM-CSF)
Macrophage colony-stimulating factor (M-CSF)
60
Where are Hematopoietic Growth Factors produced, and what do they do?
HGFs regulate proliferation, differentiation, and maturation of stem cells, progenitor cell, and precursor cells. HGFs enhance survival and functional activities of mature blood cells. They interact with specific cell-surface receptors that regulate gene expression.
HGFs are produced by activated T and B-lymphocytes, macrophages, fibroblasts and endothelial cells
61
What is cellularity?
The portion of the marrow that is hematopoietically active (red marrow). If 1/2 the marros is occupied by hematopoietic cells and 1/2 by fat, the cellularity is 50%
62
How does bone marrow cellularity change with age?
Cellularity decreases with age. After age 50, cellularity is equal to ~100-age of patient
63
Granulocytic precursors (Basophil, Neutrophil, Eosinophil)
Myeloblast > Promyeloctye > Myelocyte > Metamyelocyte > Band form > Mature cell
*Look at pictures to identify*
64
Erythroid precursors
Pronormoblast > Basophilic erythroblast > Polychromatophilic erythrobast > Orthochromatic erythrobast/Normoblast > Reticulocyte > Erythrocyte
*Look at pictures to identify*
65
What is the link between Erythropoiesis and Hemoglobin level?
The rate of erythropoiesis determines the hemoglobin level
66
What initiates erythropoiesis?
Hypoxia stimulates Erythropoietin, a hormone produced by the kidneys. Erythropoietin activates stem cells of marrow to differentiate into pronormoblasts, Increases rate of mitosis and maturation, Increases rate of hemoglobin production, Increases rate of reticulocyte release into peripheral
67
How can you distinguish the different types of Granulocytes in peripheral smear?
Neutrophils- pink granules
Eosinophils - red granules
Basophils - dark purple granules
68
Auer Rods
Rod-shaped structures present in the cytoplasm of myelobasts (granulocytes), but are ONLY seen in abnormal conditions (ie Leukemia)
69
Mast Cells
Large tissue cell resembling a basophil. Covered with IgE. Present throughout body in connective tissue, concentrated in mucus membranes of respiratory and digestive tracts
70
Where do T- Lymphocytes reside?
Early T-lymphoid progenitor cells migrate to the THYMUS where they mature. Some go back to reside in marrow
71
Where do B-Lymphocytes mature?
Maturation takes place in the BONE MARROW
72
Define Neutropenia and its clinical consequences
Neutropenia is the decrease in the absolute neutrophil count (bands and segs) below accepted norm. Varies wtih age, race, ethnicity and altitude. Neutropenia in blood may reflect a decrease in the marrow meyloid pools. This increases risk of infection!
73
What are the two major causes of neutropenia?
1. Decreased bone marrow production
| 2. Increased turnover of neutrophils
74
Examples of Decreased Bone Marrow Production Neutropenia
Kostmann Syndrome, Shwachman Diamond Syndrome, Cyclic Neutropenia
75
Examples of Increased Turnover Neutropenia
Drug induced (ie chemotheraphy), Viral infection, Nutritional deficiences (folate, B12, copper and protein calorie malnutrition, which causes ineffective myelopoiesis)
76
Kostmann Syndrome
Severe peripheral neutropenia and decrease in myeloid production. High infection risk. Often develop Myeloid Leukemia or Myelodysplastic Syndrome. Monocytosis, eosinophilia, myeloid hypoplasia. Recurrent infections within first months of life. Elastase gene mutation (ELA-1) or HAX-1 gene mutation
77
Shwachman Diamond Syndrome
Neutropenia, pancreatic insufficiency with fat malabsorption, bony abnormalities and growth delay. Inheritance is AUTOSOMAL DOMINANT. Defect in nurse cells in marrow.
78
Cyclic Neutropenia
Severe peripheral neutropenia for 5-7 days with 15-25 day cycle. Recurrent fevers, pharyngitis, gingivitis, mouth ulcers. Other times in cycle no increased risk of infection.
79
Examples of Increased Turnover Neutropenia
IMMUNE: Chronic benign neutropenia of childhood, Autoimmune neutropenia, Alloimmune neutropenia.
NON-IMMUNE: Infection, Splenomegaly/hypersplenism, Pseudoneutropenia
80
Chronic benign neutropenia
Production of antibodies that cross react with neutrophils. No increased risk for infection and neutropenia resolves after 6-54 months (av, 20 months)
81
Autoimmune Neutropenia
Antibodies to specific determinants on the neutrophil, in association with LUPUS, Evan's Syndrome or Felty's Syndrome. Antibodies to RBCs, platelets or coagulation
82
Alloimmune Neutropenia
Passive transfer of antibody from mother's circulation attacking baby's cells. Accumulation of IgG antibodies by fetus provides pool of antibodies which bind the infant's neutrophils. Lasts weeks to months
83
Treatments for Neutropenia
G-CSF dose of 3-5ug/kg to help normalize production, increase neutrophil counts and prevent infection. For antibody syndromes, IV gamma globulin may be used.
84
Leukocytosis
An increase in the total WBC, caused by infection, inflammation, non-specific physiologic stress or malignancy
85
Define the term "Left Shift"
Change in WBC that results in an increase in the number of bands and segs
86
Eosiniphilia (and causes)
Absolute count of Eosinophils >350ul. Caused by allergies/allergic disorders (asthma), Parasite infections and Drug reactions (usually allergic)
87
Basophilia (and causes)
An increase in peripheral basophils. Caused by drug/food hypersensitivity, hives, infection (RA, flu, TB), and myeloproliferative diseases like CML
88
Normal functions of Neutrophils
First response of host. Rolling, Adhesion to enothelial cells, Diapedesis through cell junctions, and chemotaxis to wound
89
Organelles/Biochemistry of Neutrophil Rolling/Adherence
Plasma membrane associated receptors. Granules containing stores of receptors. Actin cytoskeleton and accessory proteins. Abnormalities results in inability to accumulate neutrophils, recurrent infections and poor wound healing
90
Organelles/Biochemistry of Neutrophil Chemotaxis
Plasma membrane, actin cytoskeleton and accessory proteins, granules. Glycolysis for energy. Abnormalities in Fc receptors cause primary ingestion defects
91
Organelles/Biochemistry of Neutrophil Ingestion
Plasma membrane. Actin cytoskeleton. Glycolysis.
92
Organelles/Biochemistry of Neutrophil Degranulation/Killing
Plasma membrane. Actin cytoskeleton. Azurophilic and specific granules. Glycolysis. Abnormalites lead to deficient neutrophil function and altered morphology
93
Leukocytes Adhesion Deficiency I
Autosomal recessive CD18 deficiency, lack of CD11b/CD18 expression. Recurrent soft tissue infections. Poor wound healing. Caused by NEUTROPHILIA and DECREASED ADHERENCE
94
Chronic Granulomatous Disease (CGD)
Defects in 1 of 4 oxidase components. Sex linked recessive or autosomal recessive. Recurrent purulent infections with catalase positive bacteria and fungi involving skin and mucus membranes. Deep infections of organs as well. NEUTROPHILIA. Defect in OXIDASE ENZYME system.
95
Chekiak Higashi Syndrome
Formation of giant, leaky granules. Autosomal recessive CHS gene. Oculocutaneous albanism, Recurrent enfection of skin, mucus membranes and respiratory tract. hepatosplenomegaly, Neurodegeneration. NEUTROPENIA. Giant granules in all leukocytes
96
Myeloper-oxidase Deficiency
Autosomal-recessive Post-translational modification defect in processing protein. Generally healthy, but increased fungal infections when associated with diabetes. DEFICIENCY of MYELOPEROXIDASE. Defect in killing CANDIDA
97
Defects in Phagocytic Function
Very high rates of bacterial and fungal infections, especially with atypical microorganisms. Infections with catalase positive organisms in patients with CGD. Peridontal disease in children. Recurrent infection in areas of body that are in contact with the microbial world
98
Defects in Compliment
Similar bacterial infections as might be seen with antibody deficiency (H. influenza, S. pneumonia). Terminal complement deficiencies (C5-C9) see problems with Neisseria organisms
99
Screening for Phagocytes
CBC with dif, morphology, Bactericidal activity, Chemotaxis assay, Expression of CD11b/CD18, NBT dye reduction or DHR oxidation
100
Confirmatory tests for Phagocytes
Adherence to inert surface or endothelial cells (CD11b/18 measurements). Reponse to chemoattractants, Ingestion of labeled particles or bacteria, Bactericidal/candidicidal activity (O2, H202 production)
101
Screening for Complement
C3, CH50, Quantitative lgs, Lymphocyte numbers
102
Confirmatory tests for Complement
Measure specific complement components in the alternative or classical pathway. Perform a detailed evaluation of the adaptive immune response.
103
Management of innate immune disorders
Anticipate infections, Broad spectrum antibiotics (switch to specific antibiotics after dx), G-CSF at 3ug/kg/day, Transplantation with hematopoetic stem cells
104
NADPH Oxidase System
Membrane bound enzyme complex. Latent in neutrophils until activated to assemble by respiratory burst. The system generates superoxide by transferring electrons from NADPH inside the cell across the membrane and coupling to molecular oxygen to produce superoxide. Superoxide can be made in phagosomes which contain bacteria/fungi. Can spontanteously form H202 that will then generate ROS
105
Diagnostic tests for NADPH oxidase defect
Nitro blue tetrazolim chloride- Defect = no blue. More blue with more production of ROS
DHR test: whole blood stained with DHR, incubated and stimulated to produce superoxide, which reduces DHR
