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banannie's version from 2015-06-08 20:52

Fetal Erythropoisis

Question Answer
Where does RBC synthesis take place in the fetus?Yolk Sac
Liver
Spleen
Bone Marrow
[Young Liver Synthesizes Blood)
Week 3-8Yolk Sac
8-28 weeksLiver and Spleen
28 weeks+ Bone Marrow
Which bones are actively erythropoising in childhood?Sternum, Pelvis, Ribs, Vertebrae, Cranial bones, Long bones
Fetal hemoglobinHbF (2 alpha, 2 gamma):
↓ affinity for 2,3 DPG
↑ affinity for O2
Facilitates exchange
Adultssternum, vertebrae, ribs, pelvis
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Types of Hb

Question Answer
Hb Aα2 β2
Adult normal hemoglobin
HbFα2 γ2
Fetal: higher O2 affinity, lower 2,3 BPG affinity
HbSα2 β2 (β-glu --> val)
Sickle cell
HbCα2 β2 ( β-glu --> lys)
Hemoglobin C disease
HbSCHeterozygote for S and C
= Less severe than sickle
Hb Gower 1zeta2- ɛ3
Embryonic hemoglobin
Hb Bartsγ tetramer
α thalassemia
Hb Hβ tetramer
α thalassemia
Hb A2α2 δ2
β thalassemia major
Hb A1cα2 β2 +glucose
Poorly controlled diabetes (Non enzymatically glycosylated)
Methemoglobulinreversible oxidation to Fe3+
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Pathologic RBC forms

PictureCell typeAssociation
Dacrocyte (Teardrop cell)Bone marrow infiltration (myelofibrosis)
Thalassemia
Target cellThalassemia
HbC
Asplenia
Liver disease
[THAL]
SpherocyteHereditary spherocytosis
Hemolytic anemia (drug and infections)
Sickle cellSickle cell anemia
Reed-sternbergHodgkins lymphoma
Ringed sideroblastSideroblastic anemia
Macro -OvalocyteMegaloblastic anemia: B12 or Folate deficiency (also hypersegmented PMNs)
Bone Marrow failure
Howell Jolly
= basophilic remnants found in RBCs
Hyposplenia or asplenia
Helmet cell (schistocyte)DIC
TTP/HUS
HELLP syndrome
Mechanical hemolysis (prosthetic heart valve)
Heinz bodies
= Oxidized hemoglobin
G6PD deficiency
Alpha thalassemia
ElliptocyteHereditary elliptocytes
Degmacyte
(Bite cell)
G6PD deficiency
Basophilic stippling
= Denatured RNA
Lead poisoning
Anemia of chronic disease
Iron Deficiency
Thalassemias
Acanthocyte (Spur cell)
= Irregular spikes
Liver disease
Abetalipoproteinemia
Echynocyte (Burr cell)
= Regular spikes
Uremia
Rouleaux formationMultiple myeloma
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Anemia

Question Answer
Anemia in males?Hb <13.5
Anemia in females?Hb < 12.5 g/dL
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Microcytic anemia

Question Answer
↓Fe ↓% Sat ↓Ferritin ↑TIBCIron Deficiency Anemia
↓Fe ↓% Sat ↑Ferritin ↓TIBCAnemia of Chronic disease
Sideroblastic Anemia
What is iron bound to in the stored form?Ferritin
TransferrinTransports iron in the blood
Delivers to the liver and bone marrow macrophages for storage
TIBCTransferrin molecules in the blood - whether bound or not by iron
↓TIBC: ↑Iron
%satpercentage of TRANSFERRIN molecules that are bound by iron (normal = 33%)
Serum FerritinStored iron
Iron deficiency in babiesBreast milk
Iron deficiency in women?Menstruation or Prenancy
Iron deficiency in adult men?Peptic ulcer disease or Colon cancer
Iron deficiency in the old?Colon polyps/carcinoma or Ancylostoma/Necator hookworms
Esophageal web+Bright red tonguePlummer Vinson: Iron Deficiency Anemia
How does gastrectomy cause iron deficiency?Acid helps iron absorption by maintaining the Fe+2 state which is more readily absorbed than Fe+3
Why do you see an increase in TIBC when theres decreased ferritin?when ferritin is decreased, the liver pumps out more transferrin to find circulating Fe+2
Koilonychia?Spoon shaped nails: Iron deficiency anemia
Pica?Chew on weird things: Iron deficiency anemia
↑Free Erythrocyte Protoporphyrin (FEP)Anemia of Chronic disease.
Decreased available iron?Anemia of chronic disease
What acute phase reactant stores iron?Hepcidin
Defective synthesis of protophorphyrin?Sideroblastic Anemia
Iron laden mitochondria form a ring around the nucleus of RBC precursors?Ringed sideroblasts: Sideroblastic Anemia
What defect causes sideroblastic anemia?ALAS (converts succinyl-CoA to ALA)
Acquired causes of sideroblastic anemia?Alcoholism (poisons mitochondria)
Lead poisoning (inhibits ALAD and ferrochelatase)
Vitamin B6 deficiency (cofactor for ALAS)
Blue gums and colicky painLead poisoning: Sideroblastic Anemia
Where is the iron in sideroblastic anemia?Trapped in the mitochondria around the nucleus
Isoniazid causes what type of anemia?Sideroblastic Anemia: decreases vitamin B6
Defect in Globin?Thalassemia
Who gets alpha thalassemia?Asians (cis trait) and Africans (trans trait)
HbH Beta chain tetramers (HbH) that damage RBCs: Alpha thalassemia with 3 deletions
Hb BartsGamma tetramers damage RBCs: Alpha thalassemia with 4 deletions
4 alpha gene deletions cause?Hydrops fetalis
Alpha thalassemia mutationChromosome 16: deletion
Beta thalassemia mutationChromosome 11: Splice site mutation
Target cells?Beta Thalassemia
Tear drop cells?Beta Thalassemia
Who gets Beta Thalassemia?Blacks, Greeks and Italian
Crewcut appearance of skullexpansion of hematopoesis into the skull: Beta Thalassemia
Chipmunk facies?Expansion of hematopoesis: Beta Thalassemia
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Macrocytic Anemia

Question Answer
Hypersegmented neutrophilsMegaloblastic anemia
↑HomocysteineMegaloblastic anemia
MC Megaloblastic anemia?Folate deficiency
Folate malabsorption happens inJejunum: Celiacs
MethotrexateFolate deficiency
Birth controlFolate deficiency
PhenytoinFolate deficiency
High methylmalonic acidB12 Deficiency
Neurologic symptomsB12 Deficiency
Pancreatic insufficencyB12 Deficiency
Pernicious anemiaAutoimmune destruction of parietal cells: B12 Deficiency
Diphyllobothrium LatumB12 Deficiency
VegansB12 Deficiency
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Normocytic Anemia

Question Answer
Corrected Reticulocyte Count?RC x (Hct/45)
Reticulocyte count >3%Appropriate Bone marrow response: peripheral destruction
Reticulocyte Count <3% indicates?Poor marrow response. Underproduction
Extravascular HemolysisHereditary Spherocytosis
Sickle cell anemia
Hemoglobin C
Intravascular HemolysisParoxysmal Nocturnal Hemoglobinuria
G6PD Deficiency
Autoimmune hemolytic Anemia
Microangiopathic Anemia
NonhemolyticAplastic Anemia
Myopthesis
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Intrinsic Normocytic Anemia

Question Answer
Glutamic acid →Valine in beta chainSickle Cell Anemia
Glutamic acid →Lysine in beta chainHemoglobin C
Metabisulfite +Sickle Cell Anemia
Howell Jolly bodySign of Autosplenectomy: Sickle Cell Anemia
Chipmunk FaciesSickle Cell Anemia
What stimulates a vaso-occlusive crisis?Low O2
Low pH
Dehydration
DactylitisPainful swelling of hands/feet: Vaso-occulsive crisis in Sickle Cell Anemia
Salmonella osteomyelitisSickle Cell Anemia
Splenic infarctsSickle Cell Anemia
How do you treat SIckle Cell Anemia?Hydroxyurea: Increases HbF
Cause of death in Sickle Cell Anemia?Acute chest syndrome: Vaso-occlusion in pulmonary microcirculation
Confirm Sickle Cell Anemia withHb electrophoresis
Mild AnemiaHemoglobin C defect
↑MCHC ↑RDW Hereditary Spherocytosis
+Osmotic fragility%RBC lysis in solution: Hereditary Spherocytosis
Jaundice+Splenomegaly+Gall stones Hereditary Spherocytosis
Treatment of Hereditary Spherocytosis?Splenectomy
Defect in Hereditary Spherocytosis?Spectrin and Ankyrin defects
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Extrinsic Normocytic Anemias

Question Answer
↑LDH ↡HaptoglobinIntravascular hemolysis
CD55/59Paroxysmal nocturnal hemoglobinuria
Complement mediated RBC lysisParoxysmal nocturnal hemoglobinuria
Mechanism of Paroxysmal nocturnal hemoglobinuria?No GPI anchor for DAF, which normally protects RBC from complement destruction
Red urine in the morningParoxysmal nocturnal hemoglobinuria
Coombs - Hemolytic anemiaParoxysmal nocturnal hemoglobinuria
Pancytopenia and venous thrombosisParoxysmal nocturnal hemoglobinuria
Ham's testParoxysmal nocturnal hemoglobinuria
Treatment of Paroxysmal nocturnal hemoglobinuria?Eculizumab: inhibits complement
Risk factor for Paroxysmal nocturnal hemoglobinuria?AML
Bite cells and heinz bodiesG6PD deficiency (x-linked)
Back pain G6PD deficiency
Mechanism of G6PD deficiency?Can't make NADPH, Can't regenerate glutathione, Can't protect from ROS
Fava beans G6PD deficiency
IgGAutoimmune hemolytic anemia: Warm agglutinin
Coombs +Autoimmune hemolytic anemia: IgG Warm agglutinin
Drugs that cause Warm agglutinin?Penicillin and alpha methyldopa
Anemia seen in SLE?Autoimmune hemolytic anemia: Warm agglutinin
Anemia seen in CLL?Autoimmune hemolytic anemia: Warm agglutinin or Cold agglutinin
IgMAutoimmune hemolytic anemia: Cold agglutinin
Painful cyanosis of fingers and toesAutoimmune hemolytic anemia: Cold agglutinin
Triggered by Mycoplasma pneumoniaAutoimmune hemolytic anemia: Cold agglutinin
Triggered by EBVAutoimmune hemolytic anemia: Cold agglutinin
SchistocytesMicroangiopathic anemia
Causes of Microangiopathic anemiaTTP-HUS
DIC
HELLP
Artificial Heart valves
Radiation (Benzene, Chloramphenicol, Alkylating agents)Aplastic anemia
Fatty bone marrowAplastic anemia
Parvovirus B19Aplastic anemia
Fanconi anemiaAplastic anemia
PancytopeniaAplastic anemia
Purpura and PetechiaeAplastic anemia
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Bleeding disorders

Question Answer
Anti-GPIIb/IIIaITP (Immune Thrombocytopenic Purpura)
Causes of ITP?Kids: infection
Adults: SLE (chronic)
Lab findings in ITP/TTP?↓Platelet count ↑Megakaryocytes
ADAMTS 13 (vWF metalloproteinase) defectThrombotic Thrombocytopenia Purpura
Symptoms of TTP?Anemia (Hemolysis)
Renal failure
Thrombocytopenia
Neurologic
Fever
GpIb deficiencyBernard Soulier
[Adehesion]
Lab findings in Bernard Soulier↑BT
Large platelets (Big Suckers)
Mild Thrombocytopenia
GPIIb/IIIa deficiencyGlanzmann Thrombasthenia
[Aggregation]
Diagnose Glanzmann thrombastheniaRistecetin cofactor assay: Agglutination
What does vWF do?1. Platelet adhesion [BT]
2. Stabilizes coag factor 8 [↑PTT]
Lab findings in vWF disease↑PTT ↑BT
Diagnose vWF diseaseRistecetin cofactor assay: No Agglutination
Treatment of vWFVasopressin
MC inherited bleeding disorder?vWF disease
Overclotting leads to bleeding state?DIC
Causes of DICSepsis (g-)
Trauma
Obgyn
Pancreatitis
Malignancy
Transfusion
[STOP Making Thrombi!]
Diagnose DICD-dimers, Schistocytes, ↓Fibrinogen
↓PC ↑BT ↑PT ↑PTTDIC
Treat DICFresh frozen plasma
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Cancer drugs

BACD
Question Answer
ABleomycin
BVinca alkaloids and taxols
CEtoposide
DAntimetabolites
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Coagulation pathway

CBEADFGHI

 

Question Answer
Hemophilia A is deficiency inFactor VIII
Hemophilia B is deficiency inFactor IX
Vit K deficiency lowersfactors II, VII, IX, X, proteins C and S
Antithrombin inhibitsThrombin, factor IXa, Xa, XIa, XIIa
Antithrombin activated byHeparin
ATissue factor→VII→ common = X→II→Fibrin and XIII
BXII→XI→IX→VIII→common = X→II→Fibrin and XIII
CCollagen, basement membrane, activated platelets
DThromboplastin (tissue factor)
Factor II =prothrombin
PT evaluatesExtrinsic ( if this is prolonged and other is ok, that mean that VII has to be abnormal)
PTT evaluatesIntrinsic (if this is prolonged and other is ok, that means that XII, XI, IX or VIII are abnormal)
antithrombin III knocks offXII, XI, VII, X, II
EVasodilation, permeability, pain
FKallikrein
GPlasmin
Hbradykinin
Ibradykinin
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heme synth

AFBGHCIDEJ
Question Answer
Adelta-aminolevulinic acid synthase: rate limiting step
Bdelta-aminolevulinic acid dehydratase
CPorphobilinogen deaminase
DUroporphyrinogen decarboxylase
EFerrochelatase
FSideroblastic anemia (x-linked, lead poisoning also causes sideroblastic anemia)
GLead poisoning
HAcute intermittent porphyria
IPorphyria cutanea tarda
JLead poisoning
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mech of antiplatelet

ABCDE

 

Question Answer
AGP Ia
BGP Ib
CAbciximab
DAspirin
EClopidogrel
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thrombogenesis

BDCEFAHIGJ
Question Answer
ABernard Soullier syndrome
BClopidogrel, Ticlopidine
CFibrinogen
DVwF, fibrinogen
ETXA2
FGlanzmann's thrombasthenia
GVwF, thromboplastin/kinase (tissue factor), tPA, PGI2)
HThrombomodulin
IvWF disease
JVwF
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thrombolytics

ABCDE
Question Answer
ABlood activator
BAntiactivators, Aminocaproic acid
CtPA, urokinase
DStreptokinase
EAntistreplase ( preformed complex of streptokinase and plasminogen that is dissociated at the site of fibrin clot to release plasminogen)
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