Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
177 Cards in this Set
- Front
- Back
|
What are the tissues of the hematopoietic system?
|
Bone marrow and all blood corpuscles, liver, spleen, lymph nodes, thymus (tissues are embryologically related)
|
|
|
Celluarity
|
fullness of bone marrow in cells, given in percent. Starts at 100% and decreases 10% with each decade of life until 70-80y/o
|
|
|
Normal myeloid to erythroid ratio
|
3:1
|
|
|
increased production of blood cells in the bone marrow can result from :
|
infection-wbc
low tissue oxygenation- rbc mediated by growth factors |
|
|
normal production of cells in bone marrow is: (wbc, rbc, plts)
|
2.4x10^9 -wbc
1x10^10- rbc 1.75x10^11- plts ** a lot** |
|
|
Stromal matrix is composed of:
|
Stromal cells, adhesion molecules and growth factors
|
|
|
Stromal cells include
|
fibroblasts, fat cells and endothelial cells--these have nothing to do w/ hemaotpoiesis
|
|
|
Embryologic hematopoiesis locations
|
yolk sac, liver, bone marrow, spleen
|
|
|
Hematopoiesis occurs where in the first six weeks of development in the fetus
|
yolk sac
|
|
|
Hematopoiesis occurs where in the 6th to 18th wks of gestation
|
liver
|
|
|
Hematopoiesis occurs where during 18-30 wks of gestaion
|
liver and spleen
|
|
|
Hematopoiesis occurs where in fetuses from 30 wks to and 8wk old infant
|
liver, spleen and bone marrow
|
|
|
Infants > 10 wks conduct hematopoiesis in their
|
bone marrow only
|
|
|
describe the cell size when referring to erythropoiesis
|
cell size decreases with maturation
|
|
|
describe the nuclei during erythropoiesis
|
the nuclei are always round and the chromatin condenses with maturation. The nucleus to cytoplasm ratio decreases w/ maturation
|
|
|
Describe the cytoplasm during erythropoiesis
|
basophilic during immaturity, pink up as cell matures and accumulates hemoglobin. **no granules
|
|
|
Name the 5 cell stages in erythropoises before a mature RBC is formed
|
Pronormoblast, basophilic normoblast, polychromatophilic normoblast, orthochromatic normoblast, reticulocyte
|
|
|
The appearance of an RBC microscopically should show a biconcave disc with a center that appears to take up how much of the cell
|
1/3
|
|
|
Average size of rbc
|
8 microns- can squeeze down to 2 microns
|
|
|
Granulocytes include
|
neutrophils, eosinophils and basophils
|
|
|
lymphocytes include
|
T cells, Bcells and NK cells
|
|
|
Monocytes are
|
tissue macrophages
|
|
|
Neutrophils
|
AKA: polys, PMNs, segs.
Have 3 lobes separated by a thread |
|
|
Eosinophil- appearance
|
two lobes and pink granules
|
|
|
Basophil-appearnace
|
blue granules and segmented nucleus
|
|
|
Morphologic stages of the neutrophil
|
myeloblast, promyelocyte, myelocyte, metamyelocyte, band, neutrophil
|
|
|
Function of neutrophils
|
Granules contain enzymes involved in oxidative and non oxidative killing of bacteria and fungi. They circuate in the blood (circulating pool) and tumble along the endothelium loosely adhereing 9marginationg pool)
|
|
|
Function of Eosinophils
|
Parasitic infxns, allergic rxns, Vasculitis, some hematologic malignancies
|
|
|
Function of basophils
|
(mast cell) infiltrate tissue, release histamine, IgE, increased in myeloproliferative disorders
|
|
|
Role of monocytes
|
circulate in the bloodstream for 24hrs then enter tissues as macrophages. They ingest fungi, and mycobacteria and play a role in battling pyogenic bacteria
|
|
|
Lymphocyte
|
very little cytoplasm, nucleus is about the same size as a rbc... their lifespan is yrs
|
|
|
Peripheral blood distribution of lymphocytes (T, B and NK)
|
70%-T
25%B <5%NK no plasma cells |
|
|
normal vs reactive lymphocytes
|
reactive lymphocytes are bigger, have more cytoplasm than non reactive. (tend to help with viral infxns)
|
|
|
Expression of specific antigens on lymphocytes indicates
|
lineage commitment and differentiation stage
|
|
|
B cell antigens
|
CD10 CD19 CD20 CD79a
sIg k/h CD38 |
|
|
NK cell antigens
|
CD16 CD56
|
|
|
T cell antigens
|
CD3 CD4 CD5 CD7 CD8
|
|
|
TdT is
|
only present on very immature B and T cells
|
|
|
CD38 is
|
only on mature B cells
|
|
|
B cell differentiation
|
Stem, Precursor B lymphoblast, Naive Bcell, Mantle cell- Follicular B blast, centroblast centrocyte, marginal zone cell, IgG/A/E plasma cell
OR Mantle, (antigen encounter) B immunoblast, IgM memory cell |
|
|
Differentation of T cells
|
stem, precursor T lymphoblast (thymic cortex), Naive T cell (Thymic medulla), ** antigen encounter**T immunoblast, Effector T cell
|
|
|
Platelets
|
arise from megakaryocytes
|
|
|
megakaryocytes
|
large, multinucleated cells that do no circulate. Produce platelets
|
|
|
Spleen
|
Filters bllod, examines blood cells and destroys injured rbcs and those that have been sensitized by IgG and complement.
Activates complement Extremely important in helping clear encapsulated organisms (strep pneumo, H. flu, N mening) |
|
|
Splenic sequestration
|
during periods of extensive red cell damage and splenic activity, blood may enter spleena and be unable to exit
|
|
|
what percent of the population will have an accessory spleen
|
10%
|
|
|
Red pulp of the spleen contains
|
splenic sinusoids
|
|
|
white pulp of the spleen contains
|
lymphocytes around arterioles
|
|
|
blood samples can be obtained by
|
venipuncture, PICC or port
|
|
|
Coulter counter
|
machine used to get cbc
|
|
|
Normal RBC values
|
M- 4.7-6.1
F- 4.2-5.4 |
|
|
Normal HgB
|
M-14-18
F-12-16 |
|
|
Normal HCT
|
M-42-52
F-37-47 |
|
|
Normal MCV
|
80-96
|
|
|
Normal MCH
|
27-31
|
|
|
Normal MCHC
|
33-37
|
|
|
Normal RDW
|
11.5-14.5
|
|
|
Red cells are highest when?
|
at birth
|
|
|
What percentage of rbcs are Hb F at birth?
|
30%
|
|
|
When do Hb F levels decrease to a normal level of 2%?
|
3months
|
|
|
Does the number of red cells vary with age? Gender?
|
Not with age
Males values exceed females at puberty |
|
|
Hemoglobin is measured in units of
|
grams per deciliter of blood
|
|
|
Hematocrit is measured as a
|
percentage, tells you the volume of packed red cells in a given volume of whole blood
|
|
|
In general what is the ratio of hematocrit to HgB?
|
Hematocrit is 3x hemoglobin
|
|
|
MCH
|
mean corpuscular HgB- avg weight of HgB per cell
|
|
|
MCHC
|
Mean corpuscular HgB concentration-avg concentration of HgB per cell
|
|
|
If the MCH of a small rbc is normal, the MCHC will be?
|
high
|
|
|
I RDW is normal...
|
all cells are of similar size
|
|
|
If RDW is increased...
|
cell size is not known (>14.5)
|
|
|
Reticulocyte count
|
must order specifically
Methylene blue stain identifies precipitated RNA in young cells. Giemsa stain also used |
|
|
Reticulocyte appearance
|
larger than mature rbc with less central pallor
|
|
|
a differential will give values for:
|
Segs, bands, Lymphs, Monos, Eos, basos and oter
|
|
|
Normal value for platelets
|
10-20 per high powered field
|
|
|
Low MCV can be attributed to:
|
iron deficiency anemia, Hemoglobinopathies (SS, thalass), anemia of chronic disease, Copper deficiency, lead poisoning (decr heme synth) often assoc w/ lo MCH (hypochromia)
|
|
|
Basophilic Stippling: definition and indication
|
punctate basophillic precipitation of undergraded RNA. Sign of ineffective hematopoiesis **seen in lead toxicity
|
|
|
target cells are seen in association with or from
|
redundant red cell membrane/decr cell volume
-HgBopathies, thalass -iron deficiency anemia drug induced hemolytic anemia or liver disease |
|
|
Schistocytes
|
helmet cells:disseminated intravascular coagulation, TTP
cells apper to have been sliced |
|
|
Acanthocyte
|
thorn cell: liver disease, artifact
|
|
|
rouleaux fromation
|
rools/stacks of cells, cells adhere to each other due to incr amt of Ig production. Seen in Multiple Myeloma, plasma cell leukemia and infx.
Can be artifact |
|
|
Howell Jolly bodies
|
remnants of nuclear chromatin normally removed by the spleen. Seen in surgically or fxnally asplenic pts and pts on dialysis. Usu one per cell
|
|
|
Spherocytes
|
RBCS with no central pallor. seen in hereditary spherocytosis
|
|
|
Bone marrow aspirate tests
|
differential, flow cytometry (determines lineage), cytogenetics, FISH
|
|
|
Bone biopsy core tests
|
cellularity?
|
|
|
Basic Metabolic Panel Includes
|
Sodium, Potassium, Chloride, CO2, BUN, Creatinine, Glu, Calcium. Run on serum
|
|
|
Comprehensive panel includes
|
BMP plus total protein, Albumin, AST,ALT, Alkaline phosphatase, and total bili
|
|
|
SPEP
|
Electrophoresis. Serum is applied to gel , current is applied and defferent proteins move at different rates/distances along the gel. Largest peak should be albumin
|
|
|
Serum Proteins
|
Albumin (main)
Microglobulins: Alpha 1 (alpha 1 antitrypsin), Alpha 2, beta1, beta 2 (predicts change in Ig prod; used to assess disease activity of Mult Myl), Igs: IgG,M,A...E,D |
|
|
Electrophoresis of HgB
|
red cells lysed, HgB is separated and applied to gel w/ current. Diff HgBs migrate at diff speeds
|
|
|
Sickle Cell "Screen"
|
RBC mixed with reducing agent and observed under microscope for characteristic change in shpae (sickle)
|
|
|
the hemoglobin molecule is made up of
|
2 alpha chains
2beta chains (non alpha) 4 heme molecules |
|
|
heme
|
ring structre calle protoporphyrin IX. has an atom of divalnt/ferrous iron attached. Ea heme combines w/ one oxygen
|
|
|
Globin Chains
|
2pr of polypeptide (four total) Each chain has ~140aa. Change in aa sequence results in diff globin chains
|
|
|
alpha globin gene
|
located on chromosome 16. Humans have 2 copies per chromatid (alpha and gamma)
|
|
|
Beta, gamma, delta globin genes
|
located on chromosome 11
Humans have two copies of gamma (alpha and gamma) per chromatid |
|
|
Humans have how many globin genes per person?
|
4 two copies alpha and gamma
|
|
|
hemoglobin formation
|
genes transcribed to mRNA > translated to globin polypeptide chain > released into cytoplasm from ribos >each globin chain binds w/ a heme molecule> heterodimers are formed bw alpha and a non alpha chain> two heterodimers join to make tetramers = hemoglobin
|
|
|
Hemoglobin A
|
2 alpha chians and 2 beta chians, main from of HgB after birth
|
|
|
HgB A2
|
2 alpha chains and two delta chains, delta chians not expressed efficientl, normally only a small amt of HgBA2 after birth
|
|
|
HgB F
|
2 alpha chains and 2 gamma chians. in adults this is only in a few RBCs, called F cells
|
|
|
Hb A1c
|
Hb A can be post translationally modified by rxns bw various sugars and the amino groups of the globin chains. Most common is where glucose is added to the beta chain--used to monitor diabetic pts
|
|
|
Hemoglobins affinity for oxygen depends on
|
the partial pressure of oxygen
|
|
|
oxygen dissociation curve affected by pH is called
|
Bohr efect. Lo pH shifts curve to the right
|
|
|
Hb has lo affinity for oxygen at
|
low O2 tension
|
|
|
As each heme group binds oxygen it affinity
|
increases
|
|
|
High 2,3-BPG shifts curve to the
|
right bc need a higher pO2 to saturate the same amt of Hb. High BPG causes Hb to tense up and deoxygenate
|
|
|
Three things that shift the curve to the right
|
fever, acidosis, high altitude
|
|
|
Hb F and the curve:
|
Hb F has increased o2 affinity and doesnt release O2 as easily as Hb A. So, the fetus needs more Hb to adequately oxygenate tissues, this is why newborns have higher Hb values than when they are older
|
|
|
RBC metabolism
|
Embden Meyerhoff Pway
Anaerobic glycolytic pway Glucose enters rbc via facilitated membrane transport system > glu is metabolized to lactic acid > req's 2 Atp per glu >generates 4 for a net of 2ATP |
|
|
2,3 BPG
|
product of rbc metabolis. Reduces methemoglobin to hemoglobin. Fe3+ to Fe2+, oxidized to reduced iron
|
|
|
G6PD and rbc metabolism
|
most common enzyme deficiency. without it, no NADPH is formed >glutathione metabolism
leads to hemolysisdoesnt occur> H2O2 doesnt get converted to water> oxidative damage to the rbc (hexose monophoasphate shunt) |
|
|
Extravascular Hemolysis
|
takes place within macrophages outside the vascular stream
-physiological conditions -spleen -Low grade chronic hemolytic states |
|
|
Intravascular Hemolysis
|
major red cell lysis occurs within circulation
-15% of Hb metabolism follows this pway -transfusion rxns |
|
|
In splenectomized pts, where does RBC destruction take place?
|
macrophages, Liver,, bone marrow
|
|
|
Cells may be retained in the splen if
|
shape is less adaptable (spherocytes), membrane is less flexible (old), inclusions or particles stuck to the membrane: heinz bodies (dnatured Hb), or Howell jolly bodis (nuclear remnants)
|
|
|
RBCs break down into (3 things)
|
globin, iron and protoporphyrin
|
|
|
globin ultimately breaks down into
|
amino acids
|
|
|
excess iron is stored as
|
ferritin in bone marrow and liver
|
|
|
protporphyrin breaks down to
|
bilirubin which goes to the liver unconjugated, then goes to the feces as bilirubin glucuronides, then is sterobilinogen in the feces and urobilinogen in the urin (makes urin dark)
|
|
|
Haptoglobin (Hp)
|
Hb binding glycoprotein make in the liver, acute phase reactant, absent in the newborn
|
|
|
Hb/Hp complex is:
|
internalized by the hepatocyte. Globin and Hp are degraded into aa for recycling, heme is catabolized into bili and iron
|
|
|
rapid saturation of Hp and rapid clearance of Hb/Hp complex occurs during
|
massive intravascular hemolysis
|
|
|
low or absent plasma Hp is an indicator of
|
recent or ongoing intravascualr hemolysis
|
|
|
Hemopexin and Mehemalbumin
|
free excess heme is bound to hemopexin and methemalbumin and taken by hepatic receptors for catabolism
|
|
|
Hemosiderin
|
some free hb is resorbed into the proximal tubules and degraded to aa, iron and bili. In low chronic hemolysis, ferritin accumulatesin the tubular cells
|
|
|
Hemoglobinuria
|
during massive intravascular hemolysis hb appears in urine, can precipitate and cause ARF
|
|
|
Hemolytic anemia
|
shorter lifespan of rbcs, compenasatory increase in rbs production (reticulocytosis)
|
|
|
Etiology of Hemolytic anemia
|
-intrinsic red cell abnormalities
-extrinsic causes of hemolysis -immune mediated hemolysis -non immune mediated hemolysis |
|
|
Intrinsic Red cell abnormalities
|
Red cell membrane disorders
enzyme disorders, Hb disorders |
|
|
Red cell membrane disorders
|
Hereditary spherocytosis
Hereditary elliptocytosis |
|
|
Red cell Enzymer Disorders
|
G6PD deficiency
Pyruvate kinase deficiency |
|
|
Hb Disorders
|
Unstable Hb, methermoglobinemia, thalassemia, SS disease
|
|
|
Extrinsic Causes of Hemolysis
|
immune mediated hemolysis, Schistocytic hemolytic anemia (mechanical distruction)
|
|
|
Immune mediated hemolysis
|
warm reactive autoimmune hemolytic Anemia, cold agglutinin disease, paroxysmal cold hemoglobinuria
|
|
|
Schistocytic hemolytic anemia
|
hemangioma(kasabach merritt syndrome), prosthetic heart valve, microangioplastic hemolytic anemia (TTP, HUS)
|
|
|
Clinical Presentation of Hemolytic Anemia
|
Pallor, fatigue, splenomegaly, gallstones, cholecystitis, dark urine, parvovirus assoc aplasia, family hx
|
|
|
Increased nutritional Requirements of chronic hemolysis
|
Greatest requirement is for folic acid.
|
|
|
Direct Coombs Test (direct antiglobulin test)
|
Used to identify presence of Igs or complement on the surface of red cells. Sample from pt is mixed with reagent that has antibodies against human Igs and complement. If agglutination forms, test is +
|
|
|
Three patterns of IgG and comlement for a positive Direct Coombs Test
|
- IgG only on surface of RBC
- IgG and C3 complement -C3 complement on ly on surface cells, antibody on cells may be IgM |
|
|
Indirect Coombs
|
test patients serum for antibodies
-cannot do on babies -use pts serum and normal rbcs |
|
|
Warm Reactive Autoimmune Hemolytic Anemia AIHA
|
IgG mediated, extravascular clearance primarily via the reticuloendothelial system (spleen), may be ideopathic or assoc with SLE, lymphoid malignancies, immunodeficiency
|
|
|
Cold Agglutinin Test
|
IgM mediated, can be assoc with mycoplasma, EBV. Intravascualr lysis
|
|
|
Paroxysmal Cold Hemoglobinuria
|
Acute illness often after viral URI (measles, mumps, varicella, syphillis, mycoplasma)
Cause by cold reactive IgG (Donath Land Antibody). Intravascular Hemolytic anemia |
|
|
Management of Hemolytic anemia
|
observe growth and development, determine baseline Hb, follow for splenomegaly, educate family regarding risks for gallstones, parvovirus B19 aplastic crisis, folate suppl, rbc transfusions, splenectomy, cholycystectomy (if needed)
|
|
|
whole blood phlebotomy yields
|
PRBC, plts, plasma
|
|
|
Apheresis
|
same as phlebotomy (except you can get more)
White Blood cells: granulocytes, monocytes, Tcells, Stem cells |
|
|
Donation of 1 unit of Whole Blood Yields:
|
1- unit PRBC
1-unit plasma 1- unit random donor plts |
|
|
Packed red Blood Cells
|
-Transfuse 1-2 units to treat anemia (Hb <8)
-stored in fridge -can be frozen for 10 yrs |
|
|
PRBC dose
|
one unit will incr Hb by 1 g/dL, incr HCT by 3%
- in pediatric pts, 10 mL/kg will incr Hb by 2g/dL and the Hct by 6% |
|
|
Massive transfusion
|
replacement of one total blood volume (usu 10 units of PRBC) in less than 24hrs
-may be complicated by dilutional coagulopathy, hypocalcemia, hyperkalemia, arrhythmia |
|
|
Platelets
|
given to thrombocytopenic pts
stored at room temp and moving given when platelet counts are below 50, 000 or pt has fxnly abnormal platelets |
|
|
Platelet Dose
|
each unit should raise patients counts 5-10,000, with 6 units being the normal dose (six pack)
|
|
|
Fresh Frozen Plasma
|
Plasma frozen within 8 hrs of phlebotmoy, will have normal levels of factor VIII (which degrades over several days...50-80% in 5 days)
|
|
|
24 hr Plasma
|
Plasma frozen within 24hrs, used fro all plasma orders at Wake. now used interchangeably with FFP
|
|
|
Plasma collected by Apheresis is also called
|
Jumbo plasma bc it is equal to 2 units and comes from one donor
|
|
|
Plasma is indicated
|
when a pt is bleeding and needs multiple coagulation factors
|
|
|
Cryoprecipitated AHF (antihemophilic factor)
|
Transfuse 5-10 units uss to replace fibrinogen. Made from FFP. Provides a more concentrated from of fibrinogen, factor VIII, von willebrand factor, factor XIII, and fibronectin
|
|
|
H antigen
|
antigen present on all human rbcs. H alone is the O blood group. h is the precursor for A and B antigens.
|
|
|
Immunodominant sugar on h antigen
|
fucose
|
|
|
Group A
|
enzyme converts H to A by adding GALNAC. their serum should have naturally occuring anti B
|
|
|
Group B
|
H converted to B by adding GAL. Serum should have naturally occuring anti A
|
|
|
Group AB
|
no A or B antibodies in the serum. Universal plasma donor
|
|
|
Goup O
|
H is not converted. Red cells can be given to any goup. Serum should have both anti A and B
|
|
|
Rh
|
aka D antigen. Not naturally occurring. Need exposure to non slef rbcs to have an antibody response (pregnancy, transfusion, ?sharing needles?)
|
|
|
Type testing- froward and reverse
|
Forward- test patients red cells for A/B antigen
Reverse- test serum Rh- test red cell for the D antigen |
|
|
Screen Test
|
check Patients serum for other antibodies against red cell antigens- like Kell Duffy Kidd. Rh
|
|
|
Cross/ Crossmatch
|
mix patients serum with sample of donor red cells from the exact unit that we wish to transfuse
|
|
|
Direct Antiglobulin Test
|
looks fro IgG and/or Cd3 (more dangerous). used to evaluate hemolytic transfusion rxns or autoimmune hemolytic anemia
|
|
|
Hemolytic disease of the newborn
|
Mother Rh- fetus Rh+
Fetal red cell enter matrnal circulation, mother synthesizes Anti D. Anti D crosses placenta and hemolyzes fetal red cells |
|
|
erythroblastosis fetalis
|
Anemia with possible organ failure, edema(hydrops) and jaundice. Cardiac failure and liver failure. DAT+. mother has high titer of anti D. incr bili and bile in amniotic fluid. in the periph smear of baby there are spherocytes and nucleated red cells
|
|
|
Transfusion rxns
|
febrile, allergic, anaphylactic, bacterial/septic, acute/delayed hemoytic, fatal
|
|
|
Febrile nonhemolytic tranfusion rxn
|
Rise in temp of 1 degree Celsius or more occuring within 2hrs of the transfusion with no other explanation. Antibodies in pt react with donor white cells/plts or by released cytokines from stored product.
|
|
|
Acute hemolysis
|
usu ABO mismatch with complement mediated hemolysis. Serum and urine show lg amts of Hb. DIC or renal failure poss. Can be fatal
|
|
|
delayed hemolysis
|
patient develops antobody to transferred cells over a period of 3-14 days. Serum may show decr Hpt and incr bili and LDH
|
|
|
incidence of Hemolytic transfusion Rxns
|
1 in 25000
|
|
|
Signa and Sx of Hemolytic Transfusion Rxn
|
fever and chills, renal failure, DIC, back pain
|
|
|
Laboratory indicators of Hemolytic transfusion Rxn
|
DAT+, hemoglobinure, hemoglobinemia, incr LDH, incr Bili, decr Hb, decr Hpt, decr Hct, periph smear shows spherocytes and schistocytes
|
|
|
Treatment for hemolytic tranfusion rxn
|
early recognition and stopping transfusion. Fluid and BP support, prevent renal failure maintain urine output (IV fluid, diuretics, renal dopamine)
|
