Blood Banking Flashcards
Who discovered the ABO blood groups in 1901?
Karl Landsteiner
In 1869, what did Braxton Hicks recommended as a nontoxic anticoagulant?
Sodium phosphate
*1st example of blood preservation research
Edward E. Lindemann contribution
Vein to vein transfusion of blood using multiple syringes and a special cannula for puncturing the vein through the skin; 1st to succeed to do a device in performing transfusions
Unger contribution
Syringe-valve apparatus; transfusions from donor to patient by an unassisted physician became practical
1914 - Hustin reportes the anticoagulant _____
1915 - Lewisohn determined _____
- sodium citrate
- minimum amount of citrate needed for anticoagulation and demonstrated its nontoxicity in small amounts
In 1916, glucose was tried as preservative solution to enhance the metabolism of the rbc, when Rous and Turner introduced ____
Citrate-dextrose solution for preservation of blood
*1930 - function of glucose in rbc metabolism was understood
His pioneer work during World War II on developing techniques in blood transfusion and blood preservation led to the establishment of a widespread system of blood banks.
Dr. Charles Drew
In February 1941, Dr. Drew was appointed director of what?
First american red cross blood bank at Presbyterian Hospital
*pilot program he established - model for the national volunteer blood donor program
In 1943, who introduced the formula for the presevative acid-citrate-dextrose (ACD)
Loutit and Mollison of England
July 1947; landmark publication
Journal of Clinical Investigation - blood preservation
* 1947 - blood banks established in many major cities in US:0; transfusion became commonplace
What did Gibson introduced?
Improved preservative solutiom - citrate-phosphate-dextrose (CPD) - less acidic than ACD; became the standrad preservative for blood storage
Before, a single unit of whole blood could serve only one patient. But because of ______, one unit may be used for multiple transfusions
Component therapy
Amount of whole blood in a unit
450ml +/- 10% (1 pint)
* recently 500ml +/- 10% - modified plastic collection system; volume of anticoagulant-preservative soln from 63 to 70ml.
For a 11 pound donor, a maximum volume of ___ can be collected
525 ml
Total blood volume of most adults
10-12 pints
Fluid lost from 1-pint donation can be replenished for how many hours?
24hours
*donor’s red cells are replaced within 1-2 months after donation
A volunteer donor can donate whole blood every what week?
8 weeks
Units of the whole blood collected can be separated into 3 components:
Packed rbcs
Platelets
Plasma
Less whole blood has been used to prepare platelets because of what?
Increased utilization of apheresis platelets
The plasma can be converted by _____ to a clotting factor concentrate that is rich in ____
Cryoprecipitation; antihemophilic factor (AHF; factor VIII)
How many days does a unit a whole blood-prepared RBCs may be stored?
21-42 days
3 donation processes:
Educational reading materials
The donor health history questionnaire
The abbreviated physical examination
What does AABB means in AABB pamphlet?
An important message to all blood donors
*contains info on the risk of infectious diseases transmitted by blood transfusion, signs and symptoms of AIDS
It is used to identify donors who have been exposed to diseases that can be transmitted in blood (west nile virus, malatia, babesiosis, chagas dse)
The donor health history questionnaire
The abbreviated physical examination includes
Blood pressure, temp readings, hgb or hct level, inspection of the arm for skin lesions
3 areas of rbc biology that are crucial for normal erythrocyte survival and fxn:
Normal chemical composition and struc of the rbc membrane
Hgb struc and fxn
Rbc metabolism
TRUE or FALSE: even if only one area of rbc biology is defected, RBCs surviving will result in less than the normal 120 days in circulation
TRUE
RBC membrane represents a semipermeable lipid bilayer supported by a meshkike protein cytoskeleton structure. What is the main lipid component of teh membrane?
Phospholipids
Proteins that extend from the outer surface and span the entire membrane to the inner cytoplasmic side of the rbc
Integral membrane proteins
What are peripheral proteins?
2nd class of membrane proteins, located and limited to the cytoplasmic surface of the membrane forming the rbc cytoskeleton
TRUE or FALSE: lipids are equally distributed in the 2 layers of membrane
False
Biochemical composition of the rbc membrane
52% protein
40% lipid
8% carbohydrates
The loss of ATP levels leads to a decrease in the phosphorylation of spectrin and, in turn, a loss of ________
Membrane deformability
Accumulation of membrane calciym results in
Increase membrane rigidity and loss of pliability
An organ that functions in extravascular sequestration and removal of aged, damaged, or less deformable rbcs or fragments of their membrane
Spleen
*rbcs are at a disadv when they pass small (3-5um) sinusoidal orifices of spleen
The loss of rbc membrane is exemplified by the formation of _____ and ______
Spherocytes and bite cells
Cells with a reduced surface to volume ratio
Spherocytes
A cell that has a permanent indentation in the remaining cell membrane due to the removal of a portion of membrane
Bite cells
Prevents colloid hemolysis and control the volume of the rbc
Permeability properties of the rbc membrane and the active rbc cation transport
Rbc membrane is freely permeable to _____ and impermeable to ____
Water and anions (Cl, Bicarbonate); cations (Na, K)
RBC volume and water homeostasis are maintained by controlling the intracellular concentrations of sodium and potassium. The erythrocyte intracellular-to-extracellular ratios for Na and K are
1:12 and 25:1 respectively
The 300 cationic pumps, which actively transport Na out of the cell and K into the cell, require energy in the form of ATP. T or F
True
Calcium is also pumped from the interior of the rbc through _____
Energy-dependent calcium-ATPase pumps
A cytoplasmic calcium-binding protein that controls the pumps for calcium and prevents excessive intracellular Ca buildup
Calmodulin
When rbc are depleted, ___ and ___ arr allowed to accumulate intracellularly, and ___ and ___ are lost, resulting in a dehydrated rigid cell
Ca and Na; K and water
RBCs metabolic pathways that produce ATP are mainly aerobic or anaerobic?
Anaerobic because the fxn of rbc is to deliver oxygen, not to consume it
3 ancillary pathways that serve to maintain the struc and fxn of hgb
Pentose phosphate pathway, methgb reductase pathway, Luebering-Rapoport shunt
Glycolysis generates about 90% of the ATP needed by the rbc; 10% is provided by the
Pentose phosphate pathway
A defect in methgb reductase pathway can affect
Rbc post transfusion survival and fxn
In Luebering-Rapoport shunt, it permits the accumulation of an impt rbc organic phosphate
2,3-diphosphoglycerate (2,3-DPG)
* amount found withing rbcs has an effect on the affinity of hgb for oxygen and therefore affects how well rbcs fxn post transfusion
Hgb’s primary fxn
Gas transport : oxygen delivery to the tissues and CO2 excretion
The unloading of oxygen by hgb is accompanied by widening of a space between ____ and the binding of 2,3-DPG on a mole-for-mole basis, with the formation of _____ between the chains
Beta chains; anionic salt bridges
Tense form - deoxyhgb molecule. Lower affinity or high affinity for oxygen?
Lower affinity.
*relaxed form - high affinit, anionic salt bries are broken, beta chains are pulled together, 2,3-DPG is expelled
The allosteric changes that occur as the hgb loads and unloads oxygen are referred to as the
Respiratory movement
The dissociation and binding of oxygen by hgb are not directly proportional to the partial pressure of oxygen in its envi but instead wxhibit a sigmoid-curve relationship known as the
Hgb oxygen dissociation curve
The normal position of the oxygen dissociation curve depends on 3 diff ligands:
H ions, CO2, organic phosphates
*2,3-DPG - most impt
In Hgb oxygen dissociation curve, shift to the right: increased 2,3-DPG, decrease hgb’s affinity for oxygen molecule and increase or decrease oxygen delivery to the tissues?
Increase
2 criteria used to evaluate new preservation solutions and storage containers
Average 24hr post-transfusion rbc survival of more than 75%
Red cell integrity maintained throughout the shelf-life of the stored rbcs(assessed as free hgb less than 1% of total hgb)
To maintain the optimum viability, blood is stored in teh liquid state b/n what temp?
1 and 6 degrees C
The loss of rbc viability has been correlated with
Lesion of storage (associated with various biochem changes)
The rate of restoration of 2,3-DPG is influenced by
Acid base status of the recipient, phosphorus metabolism. Degree of anemia, overall severity of disorder
How many mg of iron is contained in one rbc unit?
220-250mg
Low 2,3-DPG, increased affinity for oxygen results in
Cardiac output, decrease in mixed venous blood tension
Preserving solutions that are added to rbcs after removal of plasma with or without platelets
Additive solutions
*contained in a satellite bag
Benefits of rbc additive solutions
Extends the shelf life of rbcs to 42 days by adding nutrients
Allows for the harvesting of more plasma and platelets from the unit
Produces an rbc concentrate of lower viscosity that is easier to infuse
3 additive solutions that are licensed in US
Adsol
Nutricel
Optisol
*contain saline, adenine, glucose
It allows individuals to donate blood for their own use in meeting their needs for blood transfusiopn
Autologous transfusio
Primarily used for autologous units and the storage of rare blood types
RBC freezing
RBC freezing involves the addition of ____ to rbcs that are less than 6 days old
Cryoprecipitate agent
*glycerol - most common
Usual storage temp for rbc freezing is
Below -65degrees C
2 conct of glyerol have been used to freeze rbcs:
High conct glycerol (40%w/v)*most common Low cont (20% w/v)
T or F. 10yr storage periods of rbc do not adversely affect viability and fxn
True
Advantages of rbc freezing
Long term storage
Maintenance of rbc viability and fxn
Low residual leukocytes and platelets
Removal of significant amounts of plasma proteins
Disadvantages of rbc freezing
Time consuming process
Higher cost of equipment
Storage requirements
Higher cost of product
Transfusion of frozen cells must be preceded by a ______; otherwise the thawed cells would be accompanied by hypertonic glycerol when infused, and rbc lysis would result
Deglycerolization process
Define rbc rejuvenation
Process by which ATP and 2,3-DPG levels are restored or enhanced by metabolic alterations
Only rbcs prepared from ___ml collections can be rejuvenated
450ml
Improved additive solution research is conducted for
Longer storage periods could improve the logistics of providing rbcs for clinical use
Inactivating pathogen that may be in rbc unit is more challenging than pathogen reduction. T or F
False
Mechanism for forming O-type rbcs
Use of enzymes that remove carbohydrate moieties of the A and B antigens
Creati rbcs in the lab is known as
Blood pharmin
Research on blood substitues is focused on two areas. These fxn to carry and transfer oxygen
Hgb-based oxygen carriers (HBOCs)
Perfluorocarbons (PFCs)
Original term of rbc substitute
Blood substitute
Benefits of artificial oxygen carrier
Abundant supply No need for typing and crossmatching Extended shelf life Free of blood-borne pathogens Can be stored at RT
Cellular fragments derived from the cytoplasm of megakaryocytes present in the BM
Platelets- no nucleus, mitochondria contain DNA
Platelets are released and circulate approximately for how many days? Ave diameter is ___. Normal ct ranges from ___ to ____
9-12 days; 2-4um; 150,000-350,000 per uL
Normal plt fxn in vivo requires more than
100,000plt/uL
Role of platelets in hemostasis
Initial arrest of bleeding by platelet plug formation
Stabilization of the hemostatic plug by contributing to the process of fibrin formation
Maintenance of vascular integrity
Discuss platelet plug formation
It involves the adhesion of platelets to the subendothelium and subsequent aggregation, with thrombin being a key effector of these phenomena.
3 types of storage or platelet granules
Dense granules/bodiessmaller and fewer (2-10)
Alpha granulesmost numerous
Lysosomes
Alpha granules stores a number of diff subs, such as
Beta-thromboglobulin Plt factor 4 Plt-derived growth factor Thrombospondin Factor V
Plt ADP and ATP are present in 2 cellular pools:
Metabolic pool*meets plt metabolic needs
Storage pool*located in dense granules, released when the plt is stimulated
It contains microbicidal enzymes, neutral proteases, acud hydrolases
Lysosomes
In the resting plt
___ATP prod is generated by glycolysis;
___ by oxygen consumption through the TCA cycle
15%; 85%
2 main reasons for the 5-day shelf-life for platelets
Bacterial contamination at incubation of 22 degrees C
Loss of plt quality during storage(plt storage lesion)
It often results in temporary aggregation of plt into large sheets that must be allowed to rest for the aggregation to be reversed, esp when the plt concentrates (PCs) are prepared with the plt-rich-plasma (PRP) method.
Platelet activation
Who started the first classification system of living things?
Carolus Linnaeus in the 17th century
*used the unit of “species”
In 1859, Charles Darwin published this book about the diversity of life
On Origin of Species
T or F. Natural selection is how one organism could gain an advantage over another and better survive in a given envi
True
His work make wave for the devt of science of genetics. He used sweet pea plants in his exp
Gregor Mendel
The termed used by Mendel to describe the factors that are responsible for the physical traits in his exp
Elementen
*genes within the nucleus
The 1st generation in the study of Mendel
Parental, pure, or P1 generation
The 2nd generation of Mendel’s exp
First-flial, F1 generation
Major areas of population genetics
Mendel’s laws of inheritance
Hardy-Weinberg principle
Inheritance patterns
In a pedigree analysis, males are represented by ____ and females are represented by _____
Squares; circles
A double line between a male and a female indicates
Consanguineous mating
In a pedigree, a still birth or abortion is indicated by _____; deceased family members is to _____
Small black circle; line crossed through them
_____ stains as dark bands
_____stains as ligh bands and consists of highly condensed regions that are usually not transcriptionally active
Heterochromatin
Achromatin
Swollen form of chromatin in cells which is more active in the synthesis of RNA for transcription
Euchromatin
T or F. Histones are various basic proteins
True
Human have 22 autosomes and one set of sex chromosomes, __ in female and __ in male
XX; XY
The specific lovation of a gene on a chromosome is called
Locus
Define alleles
Alternate or diff forms of the gene
T or F. Phenotype is the sequence of DNA that is inherited
False. Genotype
Phenotype is anything that is produced by the genotype
The inheritance of different alleles from each parent gives a ______ genotype
Heterozygous
It is a gene that does not produce any obvious, easuly detectable traits and is seen only in phenotypic level when the individual is homozygous for the trait
Amorph
It refers to the condition when one chromosome has a copy of the gene and the other chromosome has that gene deleted or absent
Hemizygous
Define mitosis
The process by which cells divide to create identical daughter cells
It is the phase at the beginning of mitosis in which DNA is in the form of chromatin and is dispersed throughout the nucleus.
Interphase
*cells are not actively dividing
Stage of mitosis in which chromatin condenses to form chromosomes and the nuclear envelope starts to break down
Prophase
Stage of mitosis in which chromosomes are lined up along the middle of the nucleus and paired with the corresponding chromosome
Metaphase
*chromosome preparations are made for chromosome analysis in cytogenetics
Stage of mitosis in which the cellular spindle apparatus is formed and the chromosomes are pulled to opposite ends of the cell
Anaphase
*cells become pinched in the middle and cell division starts to take place
The last stage of mitosis in which the cell is pulled apart, division is complete, and the chromosomes and cytoplasm are separated into two new daughter cells
Telophase
Resting stage between cell divisions
Interphase
In prophase, each chromosome has chromatids from duplication of DNA, and chromatids are linked via the _____
Centromere
In metaphase, chromosomes are held in place by _____ that are attached at the mitotic spindle apparatus
Microtubules
A process used to produce gametes
Meioisis
T or F. 2 unique daughter cells are formed during meiosis
False. 4
Stage of meiosis in which chromosome crossing over occurs
Prophase I
Stage of meiosis in whoch two sister chromatids separate
Anaphase I
Stage of meiosis ij whoch homologous line up at the equator
Metaphase II
Cell cycle
Gó - resting stage
G1 - prereplication stage; cells produce RNA and synthseize protein
S stage - DNA is synthesized; DNA replication
G2 - postreplication stage
Phase where cell division or mitosis occurs
M phase
Backbone of heredity
DNA
Composed of long, linear strands of DNA tightly coiled around histones
Chromosomes
Define nucleosome
Complex of DNA and histone protein
DNA is composed of
Four nitrogenous bases
5-carbon sugar molecule called deoxyribose
Phosphate group
The sugar and phosphate comprises the backbone of DN molecule. It is stabilized by
Hydrogen bonding and Van der Waals forces
The backbone of DN is joined by
Phosphodiester linkages
Purines:
Pyrimidines:
Adenine and Guanine - double ring struc
Cytosine and Thymine - single ring struc
How many hydrogen bondings does C and G have?
3 hydrogen bonds - stronger pairing
A and G - 2 hydrogen bonds
*Watson-Crick base pairing - occurs in the B-form, right handed helical struc; James Watson and Francis Crick
A type of DNA that is left handed helix with a diff 3-dimensional conformation but contains the same 4 bases
Z-DNA
The phosphates in the DNA backbone attach to the sugar at the ___ and ____ carbon atoms
Third and fifth
The linkage of the purine or pyrimidine nitrogenous base to the sugar is at carbon number
1
Define codon
Triplets of nucleotides
Codon specific for initiatipn of transcription and translation
Start codon
Replicatio
First, sections of DNA must be uncoiled and two strands must be sep
Enzyme that opens the supercoils of DNA
DNA gyrase
Enzyme that separates the two strands of duplex DNA
DNa helicase
Synthesize a new strand in the 5’ to 3’ direction on the leading strand; proofreads the addition of new bases to the growing DNa strands and can remove an incorrectly incorporated base
DNA polymerase IIII
These are proteins that interact with the open strands of DNA to prevent hydrogen bonding when it is not needed during replication
Single-stranded binding proteins
In order for replication to take place on any piece of DNA, there must first be a short _____ piece that binds to the beginning of the region to be replicated
Oligonucleotides(composed of RNA) - called primers
Small regions of newly replicated DNA
Okazaki fragments
Enzymes that joined together the okazaki fragments
DNA polymerase I and DNA ligase
RNA primers are synthesized and added to the DNA strands by an enzyme called
Primase
It joins the phosphodiester bonds of the DNA backbone
DNA ligase
It recoils the DNA
Isomerase
Type of editing where an incorrect nucleotide is removed and the correct one is inserted in its place
Mismatch repair
Type of mutation in which only one type of nucleotide is changed
Point mutation - includes substitutions, insertions, deletions
A type of mutation in which one purine is substituted for another purine. Same is true with pyrimidine
Transition
It results in a change in a codon, which alters the AA in the corresponding peptide
Missense point mutation
Results when a point change in one of the nucleotides of a DNA sequence causes one of the three possible stop codons to be formed
Nonsense mutation
Stop codons
UAG
UGA
UAA
Amber
Opal
Ochre
