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Constituents of blood
Cellular components and Plasma components
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Three main cell types of blood:
RBCs, WBCs, and Platelets
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What is serum?
Plasma w/o clotting factors
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Reduced RBC?
Anemia --> fatigue
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Reduced WBC?
Leukopenia --> infection
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Reduced thrombocytes/clotting factors?
Thrombocytopenia/hemophilia --> bleeding
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What can increased amount of cellular component indicate? (eg, leukocytosis)
Physiological response or malignant proliferation
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Increased RBC?
Erythrocytosis = Hypoxia or Polycythemia Rubra Vera
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Increased WBC?
Leukocytosis = Infection or Leukemia
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Increased thrombocytes?
Thrombocytosis = Response to inflammation or Essential thrombocytosis
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Increased clotting factors?
Hypercoaguable states
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List the three locations for blood production
Yolk Sac --> Liver/Spleen (5/6 weeks) --> Bone Marrow (5-6 months on)
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What are cytokines?
Growth factors
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What does hypoxia lead to? (growth wise)
Hypoxia --> EPO --> RBC
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What does infection lead to? (growth wise)
Infection --> GCSF/GMCSF --> Neutrophils/Monocytes
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What does hemorrhage lead to? (growth wise)
Hemorrhage --> Thromobopoeitin --> Platelets
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Two defining characteristics of hematopoietic stem cells (HSC) ?
Pluripotent and Capacity for self renewal
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What does pluripotent mean?
Capacity to generate all cell lineages (but can't fully regenerate organism)
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What does totipotent mean?
Ability to differentiate and form all cells of a complete organism
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What does quiescent mean?
Dormant (not cycling); only 5% of HSC cycle at once
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Diff between symmetric and asymmetric division?
Symmetric: parent stem cell to two identical daughters; Asymmetric: parent generates a daughter and another parent (regenerates itself)
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Put these in order: Committed CFU, Stem Cell, Colony Forming Unit
Stem Cell (pluripotent, quiescent) --> CFU (high proliferative rate, high potential, limited self renewal) --> Committed CFU (high proliferative rate, lineage specific)
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What is aplastic anemia?
Damaged bone marrow/stem cells (often result from radiation)
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What are hematologic cancers?
Clonal expansion of hematopoetic cells induced by (epi)genetic changes; Leukemia, lymphoma, myeloma.
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How do monoclonal tumours differ from polyclonal tumours?
Monoclonal tumours originate from only one crazy cell
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Describe RBC shape and why it is that way
Biconcave disc for flexibility, maximum surface area for gas exch, laminar flow
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What are the RBC roles?
Primary carrier of gases for cellular resp.; oxygen, CO2, NO; also possibly oxygen sensor
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What is the lifespan of a RBC?
120 days
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What is a reticulocyte?
A young RBC with no nucleus; 1% of red cells in peripheral blood
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If RBC count/tissue oxygenationv is low, EPO level will be....
High
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Where does EPO act and what does it do?
BFU-E and CFU-E; stimulate growth and maintain survival
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Where is EPO made?
Peritubular cells of kidney
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Describe primary Hemoglobin structure?
4 Globin chains (2 alpha and 2 beta); Each chain linked to heme protein; Each heme has an iron molecule
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What are the three types of Hemoglobin and what globin chains are they composed of?
Fetal--> 2 alphas/2 gammas; Adult 1 --> 2 alphas/2 betas; Adult 2 --> 2 alphas/2 deltas
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Where are beta/gamma globin genes?
Chromosome 11
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Where are alpha globin genes?
Chromosome 16
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What is low hemoglobin called?
Anemia
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What occurs when we have lack of globin chain due to mutation on chromosome 16 or 11?
Thalassemia
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What occurs when a point mutation lead to a val-->glu?
Sickle cell disease
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What is Hb-O dissociation curve shape and why?
Sigmoid; cooperativity between globin chains
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What modifies the Hb-O curve?
Ph, 2,3 DPG,
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List types of WBC
Neutrophil, Lymphocytes, Monocytes, Eosinophils, Basophils
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What do platelets do?
Thrombocytes form a plug when they come into contact with damaged blood vessel wall; initiate coagulation cascade
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Are platelets the smallest cell of blood?
Yes!!!!
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Do platelets circulate in active form?
No
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How long do they live and what stimulates their growth?
7-10 days; Thrombopoietin
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How much does plasma volume increase in pregnancy?
40-60%
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How much does RBC mass increase by and what is the issue with this?
20-50%; Hb concentration falls 10-20 g/L
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What is EPO stimulated by during pregnancy?
Prolactin/Progesterone
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Which of the following does not increase during pregnancy: WBC, Platelets and/or clotting factors?
Platelet count stays the same
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What are the components of plasma (BONUS: what is the biggest consituent)?
Water (95%), Proteins (albumin, gamma globulins, clotting factors), Electrolytes, Glucose, fats and minerals
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What results from a deficiency of clotting factors and what is a possible cause?
Hemophilia due to liver disease (produces all except VIII)
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What is the clinical relevance of immunoglobulin deficiency?
Increased susceptibility to infection (congenital or acquired immunodeficiency)
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What are possible causes of albumin loss?
Nephrotic syndrome (peeing it out), liver disease, protein losing enteropathies
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What is a CBC? Describe briefly how it is done
Complete Blood Count; Blood collected in EDTA, Ca++ chelator to stop clotting, place lyse/unlysed sample in automated cell counter
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What does the lysed sample tell us?
Hb concentration, WBC stuff
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What does the unlysed sample tell us?
RBC #, size (MCV), and distribution (RDW); Platelet count
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What are the most important measurements of the CBC?
WBC count, Hb conc g/L, RBC count, MCV, RDW, Platelet count
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What are some calculated (less relevant) components on the CBC?
Hematocrit (RBC x MCV), Mean cell Hb/MCH (Hb/RBC), Mean cell Hb conc/MCHC (Hb/Hct)
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