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48 Cards in this Set
- Front
- Back
What are the two models explaining the hematopoietic stem cell ontogeny in the embro and fetus?
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1. Single stem cell model
-- hematopoietic stem cells arise from the yolk sac -- migrate to the fetal liver and later to BM 2. Dual stem cell model -- hematopoietic stem cells arise during the mesoderm formation -- migrate both to the yolk sac and to intraembryonic sites (aorta, gonad, mesonephros) -- capable of self-renewal and diff in absence of growth factors as opposed to progenitor cells found in adult marrow -- shown to give rise to several mature cell types (erythrocytes, megakaryocytes, granulocytes, monocytes, anc cells of immune system) -- present in cord at birth and been shown to engraft and sustain long-term hematopoiesis in transplanted individuals |
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What are the periods that divide hematopoiesis from coception to birth?
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mesoblastic
hepatic myeloid |
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Describe the process of hematopoiesis.
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Foci of primitive erythropoiesis are identified by the 3rd to 4th week in the area vasculosa of the yolk sac
-- give rise to the blood vessels and to the primitive blood cells, hematocytoblasts First blood cells produced by the embryo are RBC series and can be seen 4-5wks post-conception. Characterized by: 1. intravasc differentiation and embryonic Hb content 2. persistence of the nucleus as they mature 3. increased sensitivity to erythropoietin: more rapid differentiation and shortened lifespan 4. megaloblastic appearance w/ MCV of 250fl/cell Normoblastic erythropoiesis begins around 6th week of gestation in the liver and by 10th week development accounts for >90% of circulating RBCs -- liver remains major site of hematopoiesis from 3rd to 6th month By second trimester, gradually shifts from liver to BM |
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What about hematopoiesis following birth?
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Amount of marrow tissue continues to grow w/o increase in cellular concentration.
To increase production: -- increase cell turnover OR -- increase volume of hematopoietic tissue producing marrow expansion mostly seen in the calveria |
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Erythropoiesis is primarily under the influence of...?
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The fetus; only partially affected by maternal factors
Erythropoietin, produced by fetal liver plays increasing role in -- hepatic and myeloid phase -- will be detectible in cord blood at birth |
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Erythropoietin levels after birth?
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Becomes almost undetectible w/in the first week of life
-- Hb synth and RBC production decline abruptly in first week of life |
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Hb content in newborns?
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Content changes composition throughout embryonic/fetal development and continues through the first few months of life
ε chain --> embryonic Hb -- declines in first trimester (by second month) γ-chain --> fetal Hb -- begins in first trimester -- peak levels 2nd and 3rd trimesters -- levels decline after birth for "Hb switch" β chain --> adult Hb -- low levels throughout gestation -- levels increase after birth for "Hb switch" (See pg 144 for chart) |
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Normal blood values for a fetus at gestational age?
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↑ Hb and Hct during pregnancy w/ stabilization at ~33wks
↓ MCV and ↓ retic count throughout pregnancy |
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Normal blood values at time of cord clamping?
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Placental vessels:
-- 75-125mL of blood (25-33% of fetal blood volume) -- delayed clamping (30-40sec after birth) ↑ both blood volume (up to 60%) and Hb level |
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Normal blood values at a sampling site?
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At birth, the cap/venous ratio is >1.0 and inversely correlates w/ gestational age
-- >1.2 in premature infants <30 wks gestation This difference disappears by 5 days life |
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List causes of anemia in neonates.
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Hemorrhage
Hemolysis Impaired RBC production |
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Causes of hemorrhage in a neonate?
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1. feto-maternal or fetal-fetal occult hemorrhage
2. obstetrical complications/malformation of placenta and cord 3. internal hemorrhage 4. iatrogenic (blood draws) |
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Causes of feto-maternal hemorrhage?
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Most common:
-- traumatic amniocentesis -- external cephalic version prior to delivery Other causes: -- traumatic injury to mother during pregnancy -- third trimester amniocentesis -- placental abnormalities -- manual removal of placenta |
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Incidence of feto-maternal hemorrhage?
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documented in 3/1000 women
Fetal cells will be present in ~50% of all pregnancies -- when present, account for less than 2mL in 98% of those pregnancies Hemorrhage ≥ 30mL have been documented in ~3/1000 women |
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Dx of feto-maternal hemorrhage?
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Depends upon the demonstration of fetal cells in the maternal circulation.
In the presence of HbF producing hemoglobinopathies in the mother and ABO incompatibility: Kleinhauer and Betke acid elucidation technique is most commonly used test -- based on the resistance of the fetal Hb to elute from intact red cells in acid medium |
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Incidence of fetal-fetal hemorrhage?
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Observed only in monozygotic multiple births w/ monochorial placentas
13-33% twin-twin transfusion in twin pregnancies -- difference in Hb btwn recipient and donor can be as high as 5g/dL |
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Result of fetal-fetal hemorrhage?
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DONOR: Severe anemia
RECIPIENT: Polycythemia w/ symptoms of hyperviscosity, DIC, and hyperbilirubinemia |
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Causes of obstetrical complications/malformations of placenta and cord?
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Rupture of cord can occur:
-- during rapid delivery -- in normal delivery when it is too short -- if entangled around fetus -- if forceps are used in difficult deliveries Velamentous insertion of umbilical cord -- rare -- 1-2% of pregnancies assoc w/ this malformation result in severe hemorrhage and perinatal death rate ranging from 58% - 80% Other causes: -- accidential incision of placenta during C-section -- placenta previa or abrupto |
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What can cause internal hemorrhage?
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traumatic delivery
vacuum extraction breech delivery VitK deficiency neonatal infection (CMV, adenovirus) hemangioma BW <1500g maternal intake of meds interfering w/ normal hemostasis maternal platelet Ab directed against fetus' platelets **anemia occurs in first 24 to 72 hours of life w/o assoc jaundice |
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Iatrogenic blood draws and anemia?
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Number of draws is inversely proportional to birth weight and gestational age
-- more premature will be sickest and require greatest magnitude of interventions Neonates <1500g lose btwn 5 and 45% of their blood volume during the first 4 weeks in the hospital Need increased number of transfusions |
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Clinical manifestations of acute blood loss in a newborn?
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acute distress
pallor shallow, rapid, irregular respiration weak or absent pulses NO hepatosplenomegaly |
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Venous pressure of acute blood loss in a newborn?
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LOW
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Lab values of acute blood loss in a newborn?
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Hb CONCENTRATION:
-- may be normal initially -- drops rapidly during first 24h of life RBC MORPHOLOGY: normochromic, macrocytic SERUM IRON: -- normal at birth COURSE: -- rapid treatment of anemia and shock to prevent death TX: -- IV fluids and blood -- iron therapy later |
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Clinical manifestations of chronic blood loss in a newborn?
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-- marked pallor disproportionate to evidence of distress
-- occasional CHF, including hepatosplenomegaly |
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Venous pressure of chronic blood loss in a newborn?
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Normal or elevated
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Lab values of chronic blood loss in a newborn?
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Hb CONCENTRATION:
-- low at birth RBC MORPHOLOGY: -- hypochromic, microcytic -- anisocytosis -- poikilocytosis SERUM IRON: -- low at birth COURSE: -- generally uneventful TX: -- iron therapy -- PRBCs occasionally necessary |
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How does hemolysis manifest?
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1. persistent increase in reticulocytes w/ or w/o anemia in the absence of hemorrhage
2. rapidly declining Hb w/o increase of reticulocytes and in the absence of hemorrhage |
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Neonates and bilirubin levels?
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For same degree of hemolysis, normal neonates will have higher rates of indirect hyperbilirubinemia (lipid soluble) than an adult counterpart
Seen in 60% of tern infants, 80% premature infants Normal newborns exhibit a mild elevation of bilirubin in the cord blood w/ a: -- gradual rise to ~8mg/dl by day 3 to 5 (5-7 in premies) -- normalization in the second week of life (second month in premies) |
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Contributing factors to higher bilirubin levels in neonates?
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1. increased production or destrucion of RBCs
-- fetal RBC has shorter life than adult RBCs 2. Physiologic hepatic immaturity in performing glucoronidation -- transferase level at birth is ~1% of adult level and reaches 5% by 3 to 4 days old 3. Overactive enterohepatic recirculation |
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Possible implications of increased bilirubin levels?
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When bili production increases perinatally:
-- rapid rise of indirect bilirubinemia --> most often in 1st 24h of life -- increased risk of developing kernicterus if not managed rapidly and aggressively |
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Describe mild hemolytic disease in a newborn/fetus.
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Indirect bili: <16-20mg/dL
No anemia No treatment required Incidence: 45-60% |
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Describe moderate hemolytic disease in a newborn/fetus.
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No fetal hydrops
Moderate anemia Severe jaundice -- risk of kernicterus Treat w/ exchange transfusion Incidence: 25-30% |
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Describe severe hemolytic disease in a newborn/fetus.
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IN UTERO fetal hydrops
-- incidence of 20-25% Before 34 weeks 10-12% After 34 weeks 10-12% Treat w/ intrauterine transfusion |
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Name two hemolytic diseases.
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1. Rh Hemolytic disease
2. ABO Hemolytic disease |
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Prevalence of Rh hemolytic disease?
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Prevalence w/in 6mos of delivery of the first Rh+ ABO compatible infant is 16%
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Immune response of Rh hemolytic disease?
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PRIMARY:
-- slow, 8-9wks -- weak -- produces IgM SECONDARY: -- rapid -- intense -- produces IgG --> crosses placenta |
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Pathogenesis of Rh hemolytic disease?
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Maternal anti-D IgG Ab (IgG1 and/or IgG3) coats fetal RBCs --> destruction
Persistent extramedullary erythropoiesis -- spleen, liver -- kidney, adrenal glands -- hepatosplenomegaly --> hepatic and cardiac failure |
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Tx of Rh hemolytic disease for the mother?
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1. Prevention of Rh immunization w/ anti-D IgG
-- 300μg after full-term delivery -- ≥100μg after 2nd trimester abortion -- 50μg after 1st trimester abortion 2. Suppression of alloimmunization -- intensive plasma exchange -- high dose IGIV |
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Tx of Rh hemolytic disease for the fetus and infant?
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1. Intrauterine transfusion
-- blood <96 hrs old irradiated to produce GVHD -- 40-50mL/kg admin in umbilical vein under ultrasound guidance 2. Exchange transfusion (prevents further hemolysis) -- Group O or ABO compatible blood used -- 1.5 - 2 infant blood volues are exchanged (130-170 mL/kg) -- 90% of RBCs are removed after 2 volumes and 70% after 1 volume -- not as good in removing bilirubin and IgG 3. phototherapy |
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Prevalence of ABO hemolytic disease?
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--Milder thatn Rh hemolytic disase and ABO incompatibility in adults
-- hydrops fetalis is extremely rare |
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Pathogenesis of ABO hemolytic disease?
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-- fewer A and B Ag on fetal RBCs
-- Anti-A and Anti-B do not bind complement on the fetal RBC mbrn -- Most Anti-A and Anti-B are IgM and do not cross the placenta -- IgG Anti-A and Anti-B cross the placenta binding to several other tissues and secretions |
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Labs of ABO hemolytic disease?
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25-30% of ABO-incompatible babies will have a weakly positive DAT on cord blood at delivery
-- often negative on capillary blood 2-3 days later |
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Tx of ABO hemolytic disease?
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Less that 2% of ABO incompatible babies will have disease severe enough to require exchange transfusion
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Do any other antibodies cayse fetal hemolytic disease?
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Striking reduction in Rh hemolytic disease has been accompanied by an increase in non-D alloimmunization
Ab associated w/ hydrops fetalis are: -- Anti-Kell -- Anti-c -- Anti-Fya |
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What are the causes of impaired RBC production in a fetus/neonate?
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1. physiologic anemia of prematurity
2. Diamond-Blackfan syndrome 3. Others: -- Pearson's syndrome, Leigh disease, Kearns-Sayre syndrome -- Congenital infections --> CMV, rubella, adenovirus, parvovirus -- Congenital leukemia, Down's syndrome, etc. |
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Describe physiologic anemia of prematurity.
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1. ↓↓ RBC mass > expanding plasma volume
2. Combination of physiologic shutdown of hematopoietic activity soon after birth and accelerated destruction of immature RBCs -- Hb as low as 11.4g/dL in full-term infang at 8-12wks (normal) -- Hb of 8.0g/dL at 4-8 wks for premature infants <1500g |
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Treatment for physiologic anemia of prematurity?
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Erythropoietin (r-HuEPO) is as effective as allogeneic blood transfusion in increasing Hb level, but much more costly
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Describe Diamond-Blackfan Syndrome.
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25% of affected patients are anemic at birth
-- Hb <10g/dL -- reticulocytopenia Physical anomalies in 30% -- short stature is most common -- others: microcephaly, cleft palate, triphalangeal thumb, eye anomalies Inheritance is uncertain |