ClinLab Block 4 Flashcards
How much blood do males and females have?
M- 5-6L
F- 4-5L
What are the three general functions of blood?
Transportation
Regulation
Protection
What are the three parts of centrifuged blood?
Plasma- 55% water liquid extracellular matrix
REBs- 45%
Buffy coat- WBCs and platelets
What are the percentages of WBCs in blood volume?
Neutrophils: 60-70% Lymphocytes: 20-25% Monocytes: 3-8% Eosinophils: 2-4% Basophils: 0.5-1%
What are the two functions of bone marrow?
Supply peripheral circulation with mature cells
Increase production if hematological conditions warrant
How do cells enter the blood stream?
Define Polychromasia
Sinusoids
Immature cells referred to as reticulocytes and staines w/ supra vital stain
Formed elements do not divide once they leave the red bone marrow with what exception?
Lymphocytes
What is the normal Erythroid/Granulocyte ratio?
What causes the ratio to increase?
1 : 3
Anemia
Define Stem Cell Pools
Stems cells with high self-renewal capacity and committed CFUs
Define Bone Marrow Pools
Cells stored for later release into peripheral circulation
Define Peripheral blood pools
Functional cells and storage forms of platelets and granulocytes (marginating granulocytes)
Define Hematopoieses
Production, development, differentiation, and maturation of ALL blood cells
What are the fates of myeloid and lymphoid stem cells?
M- give rise to RBCs, platelets, monocytes, neutrophils, eosinophils and basophils
L- lymphocytes
Hemopoietic growth factors regulate ? and ?
What stimulates each and where is the factor made?
Differentiation and Proliferation
Epo- RBCs, kidney
Thrombo- platelets, liver
CSFs and Interleukins- WBCs
Where is Erythropoietin and Thrombopoietin synthesized what cell do they exert their effect on?
E- kidney, RBCs
T- liver, platelets
Define Cytokines, Interleukins, and CSFs
Chemical signals responsible for promoting a specific lineage of cell
What is that pathway of events that causes increased production of blood cells?
Receptors: Dec O2 sensing in kidney
Input: inc erythropoietin released in blood
Control Center: proerythroblasts in red bone marrow mature into reticulocytes
Output: Reticulocytes enter circulation
Effector: larger number of RBCs in blood and sensed by kidneys
What stimulates the release of erythropoietin and what happens in the developmental steps?
Hypoxia
Red marrow w/ proerythroblasts who eject nucleus and become reticulocytes who develop into RBCs in 1-2days
What parts of erythropoietin cell development are erythropoietin or iron dependent?
Fe- Erytheroblasts and Reticulocytes
Eryth- everything before and including erythroblasts
What is Hgb composed of?
2 alpha and 2 beta chains
Oxygen affinity to Hgb A primarily depends on what three factors?
Temp
pH
2,3-BPG concentration
Difference between Ferrous and Ferric Iron
Which process is required for Fe metabolism?
Ous- 2+ reduced
Ic- 3+ oxidized
Redox change
How is Fe transported in the blood?
As Hgb, can not be exchanged
Transferrin bound
What makes up the Heme structure and what is it called?
If Fe is added to it what does it become?
C H N
Protoporphyrin IX
Fe2 added= Ferroprotoporphyrin
What types of Hgb are formed in a yolk sac?
What are the four types of Hgb chains that can be formed in fetus and adults?
Epsilon and Zeta
A B G D
Normal Hgb has _ globin chains
What makes up Hgb F and where is it seen?
4
A2G2- predominant formed during liver/marrow erythropoiesis in fetus
All adult normal Hgb is formed as ?
Tetramers
HbA- A2B2
HbA2- A2D2
HbF- A2G2
What are the two hemoglobinopathies listed
Thalassemia: Underproduction of normal globin proteins/lack of synthesis of chains resulting frommutated genes
Qualitative Disorders: Sickle cell dz resulting from point mutation of glutamic acid to valin in globin gene
How long do RBCs live for and where are they broken down?
120 days
Spleen and liver
RBCs that are broken down end up in what three things with what end fates?
Globins aa- reused
Fe- reused
Non-iron heme- urobilin in urine or brown stercobilin in feces
RBCs broken down in the liver release Fe3+ to be carried by transferring to ? to be combined with ?
Red bone marrow
Fe3 + Globin + B12 + Erythopoietin
What are the 4 functions of the spleen?
Filtration- spherocytes
Reservoir- 1/3 of platelets/granulocytes
Immune role- opsonizing Abs/processing Ags from encapsulated organs
Hematopoietic role
What are the three zones of the spleen and their functions?
Red pulp- RBC filter
White pulp- lymphocyte processing
Marginal zone- storage of lymphocytes and platelets
Define Spherocytes and where they’re made
Produced in spleen if RBC membranes are less deformable or if Ab coated
Spleen can produce what 3 cells if necessary?
WBCs
RBCs
Platelets
What type of lab result/finding signals PTs had a splenectomy?
Abnormal RBCs called inclusions present in peripheral circulation
What are the Granular and Agranular Leukocytes?
Granular- myleopoiesis/ granulocytopoiesis- neutrophils, eosinophils, basophils
Agranular- lymphocytes, except NK and Monocytes
How long do WBCs live for?
What is the exception?
Hrs to days
Lymphocytes live for months to years
Monocytes live for months
What WBC process is a normal response to invaders?
Which WBC process is never beneficial?
Leukocytosis
Leukopenia
Constituents and function of Neutrophil
Myeloperoxidase
Lysozyme
Defensins
Phagocytic and Microbicidal
Constituents and function of Eosinophils
Major Basic Protein
Histaminase
Helminth killing
Modulation of immediate hypersensitivity
Constituents and function of Basophils
Histamine
Immediate hypersensitivity
Constituents and function of Monocytes
Lysozyme
Phagocytic (macrophages) Ag presentation (dentrites)
Constituents and function of T-lymphocytes
Perforin
Granzye (only CD8)
Helper/suppressor (CD4)
Cytotoxic (CD8)
Constituents and function of NK Lymphocytes
Perforin
Granzyme
Cytotoxic
Which two WBCs are active phagocytes?
Neutrophils and Phagocytes, attracted by chemotaxis
What WBC responds most quickly to tissue damage?
What function do they carry out?
Neutrophils
Use lysozymes, strong oxidants and defensins to destroy bacteria
What WBC is the second to arrive to the site of tissue damage?
Monocytes are slower than neutrophils but arrive in larger numbers and destroy more microbes, enlarge and differentiate into macrophages
What WBC responsds to the sites of inflammation?
What chemicals are released?
Basophils
Heparin, histamine and serotonin to intensify inflammatory reaction
Define Emigration and what name it was formerly known by
WBCs leaving the blood stream by sticking to and squeezing between endothelial cells
Formerly known as diapedesis
What WBC are the “major” soldiers of the immune system?
Lymphocytes
What are the 3 types of lymphoctes and their functions?
B Cells- destroy bacteria and inactivate toxins, form plasma cells to produce Abs
T Cells- attack viruses, fungi, transplanted and cancer cells
NK Cells- attack infectious microbes and tumor cells
What does a Normal Plasma Cells come from?
What do plasma cells make?
Evolves from B Lymphocyte
Immunoglobulins
What is each immunoglobulin made of?
4 polypeptide chains
2 heavy chains- G A M E D
2 L chains- K L
What do myeloid stem cells develop into?
Megakaryocytes- splinter and are wrapped in plasma membrane to help stop blood loss via platelet plug formation but only live for 10 days
What are the 3 types of anticoagulants primarily used in the hematology lab?
EDTA
Heparin
Sodium Citrate
Characteristics of the EDTA tube
Lavender top
Chelating agent for Ca
Most frequent use for CBC
Excessive causes RBC shrinkage
What are the characteristics of the Green Tube
Heparin, used as an in vivo anticoagulant therapy
Binds to antithrombin 3 to catalyze the inhibition of thrombin
Define the Osmolality Fragility test?
Blood drawn in green tubes to detects whether RBCs are more likely to break down
Used to detect hereditary spherocytosis and thalassemia
What are light blue blood tubes used for?
Sodium Citrate precipitates calcium to an unstable form
Used in in coagulation studies- PT, aPTT, TT
What is measured in a CBC?
RBC count w/ morphology Hbg Hct WBC count w/ differential Platelet estimate RBC indices- MCV, MCH, MCHC, RDW (RDW technically not an RBC index)
What is one of the most common lab tests ordered?
CBC- performed by lab techs to provide info on PTs blood
What is the Rule of 3?
RBC x 3= Hgb
Hgb x 3= Hct
What causes Leukocytosis
Infections Leukemia Pregnancy Neoplasms Pneumonia Inflammation Necrosis
What causes Leukopenia
Marrow failure Radiation Chemo HIV Viral disorders
Define Total Red Blood Cell count
Count of the number of circulating red blood cells in 1mm3 of peripheral venous blood
Define Hemoglobin
Index of the oxygen carrying capacity of the blood
Define Hematocrit
% of total blood volume that is made up of RBCs
What can cause an abnormal Hct?
Anemia Bleeding RBC destruction Leukemia Malnutrion Over hydration
Define Red Cell Indices
Calculated from RBC, Hct, and Hgb
Important for classifying anemias by giving quantitative measurements of average size, Hgb content and concentration
What are the four things a Red Cell Indices provides and what are the definitions of those acronyms?
MCV- mean volume
MCH- mean Hgb
MCHC- mean Hgb concentration
RDW- red cell distribution width
Define MCV
Avg volume/size of a RBC from volume of packed RBC Hct and number of RBCs
Helps Dx types of anemia
Define MCH
Content/weight of Hgb in the average RBC by deviding Hgb by RBC count and should always correlate with MCV and MCHC
Define MCHC
Avg Hgb concentration/color in given volume of packed RBCs
MCH as high as 50= ?
MCH as low as 20=?
Macrocytic anemia
Hypochromic microcytic anemia
MCHC <32= ?
Increases are seen in ? condition?
Hypochromasia
Spherocytosis
Define RDW
Measurement of degree of anisocytosis and poikilocytosis
Define CBC w/ Differential
% of each type of leukocyte present in specimen is measured
Define CBC w/ Differential WBC
Measures functional status of immune system
Define CBC w/ Differential Segmented Neutrophils
Majority at 54-62%
Polymorphonuclear leukocytes and mature phagocytes that migrate through tissues to destroy icrobes
Define CBC w/ Differential band forms
Peripheral leukocytes w/ U shaped nucleus or curled rods prior to segmentation
Define CBC w/ Differential Basophils
Granulocytes that participate in immediate hypersensitive reactions
Define CBC w/ Differential Eosinophils
Mature granulocytes that respond to parasitic infections, eczema, and allergic/asthma reactions
Define CBC w/ Differential Lymphocytes
Large NK cells and small T/B Cells
Define CBC w/ Differential Manocytes
Large phagocytes of peripheral blood w/ an immature macrophage stage
Define Poikilocytosis
Define Anisocytosis
Increased variation of the SHAPE of RBCs
Increased variation of the SIZE of RBCs
Define Pelger-Huet Anomaly
Congenital autosomal dominant disorder where granulocyte nuclei fail to segment normally but funtions normally
Homozygous= round nucleus
Heterozygous= bilobed nuclei resembling bands
Define Toxic Granulation
Found in severe inflammatory states
Toxic granules are azurophilic and usually found in promyelocytes, metamylocyte, band and segmented stages
Due to impaired cytoplasmic maturation
Define Hypersegmentaiton
Presence of abnormally increase nuclear lobulation and one of the FIRST hematologic abnormalities seen in megaloblastic anemia
AKA myeloid right shift
Hypersegmentation may accompany other disorders of maturation such as ?
Fe deficiency
When is a RBC, Hgb, and Hct level seen increased and decreased?
Polycythemia
Anemia
When is a MCV and Mean Corpuscular Hgb level seen increased and decreased?
Macrocytic anemia
Fe deficiency, thalassemia
When is a MCHC level seen increased and decreased?
Spherocytosis
Fe deficiency, thalassemia
When is a RDW level seen increased and decreased?
Anisocytosis Fe Def>Thalassemia
No Dz known
When is a Platelet counts increased and decreased?
Inflammation, Infections, Myeloproliferative d/o
ITP, DIC, Marrow failure
When is a Neutrophil Count increased and decreased?
Infection, Inflammation, Leukemia
Inc risk of bacterial fungal infections
When is a Lymphocyte Count increased and decreased?
Infectious mononucleosis, pertussis, CLL, ALL
Acute viral infection, Sepsis, Corticosteroid therapy, Stress, Congenital Immunodeficiency
When is a Monocyte Count increased and decreased?
Chronic Inflammatory/inflammation, CMML
Hodgkin Lymphoma
When is a Eosinophil level seen increased and decreased?
Allergy, Parasite infection
Corticosteroids
When is a Basophil level seen increased and decreased?
Sinusitis, Myeloproliferative disorder
Hyperthyroid, Pregnancy
When is a Reticulocyte level seen increased and decreased?
Hemolysis, Blood Loss
Marrow Failure
How will a clotted blood sample alter the results?
Falsely low cell count
When would a hemolyzed blood sample be accepted by the lab?
Evaluating condition of intravascular hemolysis
How doe plasma factors effect an ESR time?
Accelerated w/ elevated levels of ifbrinogen and globulin proteins which decrease zeta potential that holds RBCs apart
Dec zeta= rouleaux formation and rapid sediment time
What red cell factors effect an ESR?
Abnormal shape hinder rouleaux and slows ESR
Anemia increases due to dec RBCs that favors rouleaux formation
Microcytic are slower than macro
What are the clinincal uses of ESRs?
Sickle Cell
Osteomyelitis
Stroke
CADz
ESRs are markedly elevated in ?
Hyperfibrinogenemia
Hyperglobulinemia
Monoclonial blood protein d/o- multiple myeloma
ESRs are moderately elevated in ?
Active inflammatory diseases- RA, chronic infections, collagen dz, neoplastic dz
Not Dx, useful for monitoring
Define Anemia
What are the two methods for classifying anemia?
Sx of a conditions that reduces the O2 carrying capacity of re body
Morphology, Physiologic cause/mechanism
Define Aplastic Anemia
Aplastic anemia resulting from injury to blood stem cells that leads to pancytopenia
Define Hypoproliferative Anemia, how does it present and what Dzs does it cause
Deficient EPO or marrow response
Presents w/ normocytic/chromic RBC indices but inappropriately low reticulocyte response
Includes acute/chronic inflammation, malignancy renal Dz, protein malnutrition, endocrine deficiency, anemia from marrow damage
Elevated and decreased reticulocyte counts mean?
Inc= increased damage Dec= hypoproliferative
Define Reticulocyte
Immature RBCs that have lost nuclei but not cytoplasmic RNA
What value does a Retic Count have?
Index of RBC production by marrow
Inc= reticulocytosis, means body has inc need for RBCs somewhere
Assists w/ Dx hypoproliferative anemia from anemia due to inc RBC destruction
What does a decreased retic count mean and where is it seen?
Chronic Iron deficiency anemia Aplastic anemia Ineffective erythropoiesis Thalassemias Sideroblastic anemia
What lab test is important for the classification of all anemias?
Red Cell Indices
What is Microcytosis associated with?
Small RBCs and MCV less than 78fL Fe deficient anemia Thalassemia Sideroblastic anemia Anemias of chronic diseases
What are macrocytosis anemias associated with?
Macroctyes- large RBCs >9um or MCV >100fL Liver Dz B12 deficiency Folate deficiency Neonates
What is hypochromic microcytic anemias associated with?
Thalassemias
Sideroblastic anemia
Among most common seen typically seen w/ Fe deficiency: Celiac Dz, chronic bleeds, pregnancy
Low MCV, MCH, MCHC
What part of the blood can be used to measure all iron in the body?
Serum, exhibits diurnal variations
Define Total Iron Binding Capacity
Measures total amount of iron that can be bound by transferrin in the plasma or serum
Define Transferrin Saturation
Max amount of Fe bound in plasma or serum
Less than 16%= deficient
Often increased w/ Fe overload
What part of the blood is proportional to the amount of stored iron?
What part is inversely proportional?
Ferritin- much better assessment of iron stored in the body
Serum Transferrin Receptor
Serum iron is only clinically useful if/when ?
Grossly abnormal- poisoning
Low total serum iron measurements are associated with ? conditions?
High levels ?
Deficiency, acute/chronic inflammation, pre-menstrual
Overload, pregnancy, ingestion
Where is transferrin synthesized and how many irons does it carry?
Liver
2 Fe3 molecules
What is measured as a marker of iron status?
Transferrin
What is a routine blood test used to determine iron status?
Total Iron Binding Capacity
High= low stores, high estrogen
Low= high storage, malnutrition, liver dz
What is the best serum marker of increased body iron?
What other purpose does is have?
Transferring saturation
Screens for iron overload
Define Ferritin
Protein-iron complex found in all tissues and particularly in Liver, Spleen, Skeletal muscle and Marrow
What is the single most useful test for assessing total body iron stores?
Ferritin
Low= deficient (high specificity)
High= overload
What type of lab result would come back in a PT w/ anemia of chronic disease/inflammation?
Low serum iron
Low TIBC
High ferritin
What type of conditions result would cause a PT to have anemia of chronic disease/inflammation?
Infections- AIDS, TB, malaria, chronic abscess
Inflammation- RA, Lupus, IBS
Malignancy- CA, MM, lymphoma
What causes Normochromic Normocytic anemia
Acute blood loss Inc plasma volume Aplastic anemia Neoplasm Malignancy
What causes megaloblastic macrocytic anemia?
Dec B12 and Folate- pernicious anemia due to inability to absorb B12 from dec intrinsic factor
MCV greater than 110
What effect does lack of B12 have on the body’s processes?
Disrupted DNA syntheises and ineffective erythropoiesis
In the anemia flow chart, low levels of MCV and MCHC mean ?
Issues: Serum Iron, TIBC, Ferritin
Low iron= deficiency, chronic dz anemia
Normal= do electrophoresis for thalassemias
High= examine bone marrow for sideroblastic anemia
In the anemia flow chart, normal levels of MCV and MCHC mean ?
Acute blood loss Hx
Autoimmune hemolytic anemia
Anemia of chronic dz/infection
In the anemia flow chart, high levels of MCV means ?
Check B12 and Folate levels
Low B12= Pernicious anemia, sever malnutrition, GI problem
Low folate= malnutrition, GI problem, liver dz
Normal or High of either= myeloproliferative dz, liver dz, CDA
Define Hemolytic Anemia
Shortened red cell survival
What are the intracorpuscular and extracorpuscular defects of hemolytic anemias?
Intra- Hereditary
Extra- immune, infection, splenic sequestration
People with defected red cell membranes typically present with what S/Sxs?
Anemia
Jaundice
Splenomegaly
Define Hereditary Spherocytosis
Mutations on gene that causes half of all hereditary spherocytosis
What type of lab results will be seen in PTs w/ defected red cell membrane hemolytic anemia?
Mild anemia Normal HCV and MCH MCHC elevated Decreased haptoglobin Inc osmotic fragility
What would be the lab findings in a blood sample of a TP with Hereditary Elliptocytosis
Mild compensated anemia Slight reticulocytosis Normal MCV and MCHC Decreased haptoglobin Inc osmotic fragility
What would the lab findings be on a PT blood sample with Hereditary Stomatocytosis
Mild anemia Inc MCV Dec MHCH Dec haptoglobin Inc osmotic fragility
What is the issue with G6PD deficiency
G6PD protect Hgb from being oxidized
Heinz bodies are present in RBCs due to the oxidation of hgb
What types of drugs are oxidizing drugs and will adversely effect G6PD PTs?
Anti-malarials
Sulfonamides
Nitrofurantoin
What races are more prone to G6PD deficiencies?
Greek, Italian, Jewish, Blacks
Define Hemoglobinopathies
Qualitative or quantitative abnormalities in Hgb synthesis
What are Hgb F, A and A2 made up of?
F= two A and two G A= two A and two B A2= two A and two D
What characterizes Sickle Cell Disease?
What are the two types?
Production of HbS- a Beta chain abnormality substiution of Valine for Glutamic acide in 6th position of NH2 terminal end of B chain
Homozygous= HbSS, SCDz
Heterozygous= HbSB SC trait
Define a Drepanocyte
Crescent shaped RBCs in SCDz from liquid crystals from PT becoming dehydrated, infected of low O2
Define Thalassemia
Hgb defects due to autosomal co-dominant mutation/deletion in A or B chains leading to reduced synthesis of A or B chains
Table on
Table on
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How many red, white and platelet cells are made each day?
One pluripotent stem cell can produce _ mature erythrocytes
200 billion red, 10 billion white, 400 billion platelet
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Increase of neutrophils is consistent w/ ?
Increase of bands in particular is suggestive of ?
Bacterial infections
What is the response to hemorrhage?
Hemostasis- process that causes bleeding to stop and first stage of wound healing
What is the sequence of responses that stops bleeding?
Vascular spasm
Primary hemostasis- plug formation
Secondary hemostasis- clotting
What are the two stages of hemostasis?
Primary- response to vascular injury and produces plug
Secondary- enzymatic activation of coagulation proteins to produce fibrin
What is produced and secreted from the endothelial lining of vessels?
vWF, fraction of Factor 8
Secretes prostaglandins, plasminogens activators
What are the 3 stages of plug formation?
Adhesion
Activation
Aggregation
How does aspirin effect platelet function?
Inhibits cyclo-oxygenase enzyme preventing platelets from extending pseudopods
What is the general rule about abnormalities in primary hemostasis?
Result in hemorrhage from mucosal surfaces and prolonged bleeding times after venipunctures
How is bleeding time calculated?
PFA100 w/ cartridges that have collagen/epi or collagen/ADP
How is aspirin induced platelet dyfunction deduced?
Col/Epi closure time is prolonged but Col/ADP results are normal
What does it mean if both Col/Epi and Col/ADP are prolonged?
Anemia
Thrombocytopenia
Significant platelet function defect
What does Bleeding Time measure?
Time required for cessation of bleeding after a capillary puncture
Focuses on number of platelets present and ability to form a plug
Bleeding time tests are rarely ordered but show a greatest risk for bleeding problems when time is greater than ?
15min
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