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83 Cards in this Set
- Front
- Back
What is erythropoiesis?
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The process of red blood cell formation
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Generally, what is the balance between creation and destruction of RBCs? What's the turnover rate?
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Equivalent
1% |
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What's the main stimulus for erythropoiesis?
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O2 deficiency
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What's the sensor in oxygen deficiency that causes erythropoiesis?
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The kidney
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What system removes old RBCs from the circulation?
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Reticluendotheilial system
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What is hemolysis?
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Accelerated destruction and/or clearance of RBCs
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What are the secondary effects of hemolysis?
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Decreased O2 delivery to tissues--> hypoxia --> erythropoietin --> increased RBC production by marrow
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What's typically released from RBCs during hemolysis?
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Hgb
LDH |
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What protein does free Hgb bind to in the serum?
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Haptoglobin
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What is the breakdown product of hemoglobin?
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Iron + unconjugated bilirubin
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What are the laboratory findings during hemolysis?
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Elevated serum free Hgb
High serum LDH Low serum haptoglobin High unconjugated bilirubin High reticulocyte count |
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What are some of the ways that bilirubin is excreted?
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Fecally: urobilinogen
Urine: urobilinogen |
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What is the pathway that bilirubin takes to be excreted?
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1. Breakdown in blood
2. Unconjugated bilirubin (or bilirubin conjugated to Z protein,glucuronic acid) transported toliver 3. Enters biliary system 4. In small intestine broken down by a bacterial protease 5. 90% excreted inFECES If lots and lots of bilirubin, you can have excretion in the kidney |
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What is the definition of compensating hemolysis?
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Hemolysis without anemia/mild decrease in Hg
Accelerated destruction is matched by increased production |
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How much of the RBC volume can the marrow compensate for?
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10%
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What is the definition of a hemolytic anemia?
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The destruction of RBC >> production
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What are the different types of congenital anemias?
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Sickle cell
Thalassemia Spherocytosis G6PD deficiency |
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What are some of the different types of acquired hemolytic anemias?
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Autoimmune hemolysis
MAHA Drug induced |
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What are some of the differences that you'll find between an intravascular hemolytic anemia and extravascular?
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Intravascular: hemoglobinemia, hemoglobinuria, consumption of the haptoglobin
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What are some of the intrinsic causes of hemolytic anemias?
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RBC membranes
RBC cytoplasmic enzymes Abnormal Hgb |
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What are some of the extrinsic factors that can cause hemolytic anemias?
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Acquired coditions
Oxidation Immune-mediated Mechanical destruction |
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What are some labs that you should order up to determine the etiology of a hemolysis?
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Blood smear
Hgb electrophoresis RBC fragility test RBC enzyme level assay Specific mutation studies Coomb's test |
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What congenital hemolytic anemias show abnormalities in hemoglobin? What's the test for this?
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Thalassemias
Sickle cell disease Test: Hgb electrophoresis |
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What congenital hemolytic anemias show abnormalities in the RBC membrane? What's the test for this?
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Hereditary spherocytosis
Hereditary elliptocytosis Test: osmotic fragility test |
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What congenital hemolytic anemias show abnormalities in RBC enzymes? What's the test for this?
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G6PD deficiency
Pyruvate kinase deficiency Test: enzyme levels |
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Where are the thalassemias typically found?
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Where malaria is endemic
Possibly protective |
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What are the different kinds of hemoglobin chains found?
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Alpha
Beta Gamma Delta |
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What are the types of hemoglobin that are normally found in adults?
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Hg A: Alpha2, Beta2 (96-98%)
Hg A2: Alpha2, Delta2 (2-3%) Hg F: Alpha2, Gamma2 (0-1%) |
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How many copies of each of the Hgb genes does each person have?
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Beta chain: 2 copies
Alpha chain: 4 copies |
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What are the different kinds of thalassmias?
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Beta
Alpha |
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What types of mutations typically cause the thalassmias?
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Point mutations
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What does a peripheral blood smear look like for a thalassemia?
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Hypochromia
Microcytosis Also, you can have hemolysis |
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Who typically gets beta thalassmias?
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Mediterannean people
Africans |
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What type of a mutation happens in Beta thalassemias?
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Mutation; not a deletion
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What are the different subtypes of beta thalassemias?
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2 phenotypes:
Thalassemia beta minor (trait): heterozygous Thalassemia beta intermediate: homozygous mutated; not as severe Thalassemia beta major: homozygous mutated; very severe |
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What are the symptoms of thalassema beta major?
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Severe anemia
Multi-organ failure at a young age |
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What population does not show the effects of a beta thalassemia?
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Fetus/infants:
Switching to the beta chain causes the symptoms to come out. |
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What are the findings on Hg electrophoresis in beta thalassemias?
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HgA is decreased
HgA2 is mildly increased HgF is mildly increased |
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What are the typical numbers for Hg in a person who is normal, trait, and major?
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What are the subtypes of alpha thalassemia?
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Silent carrier: "-a/aa"
Thal-alpha trait: "-a/-a" OR "--/aa" Hg H disease: "--/-a" Hydrops fetalis: "--/--" |
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What are the findings in thal-alpha trait?
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"-a/-a" OR "--/aa"
Mild decrease of alpha chain production No "new" Hg Mild anemia/low-normal Hg Marked microcytosis (decreased MCV) |
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What are the findings in HgH disease?
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"--/-a"
Severereduction in alpha chain production Hg (4 beta chains); decreased O2affinity Mild-severe hemolytic anemia Hg Bart's (4 gamma chains) in infants; severe disease |
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What are the findings in hydrops fetalis?
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"--/--"
Absence of alpha Intrauterine hypoxia Hg bart's: 4 gammas Not compatible with life |
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What's the pattern of hemoglobin amounts in the alpha thalassemias?
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What are the typical lab findings in someone with a thalassemia?
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Microcytosis +/- anemia
Hemolysis Hg electrophoresis findings Positive FH Molecular genetics confirm |
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What are the findings of thalassemias on peripheral blood smears?
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Microcytosis
Hypochromia Target cells Heinz bodies |
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What's the treatment for thalassemias?
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Chronic transfusions
Folic acid supplementation BOne marrow treatment |
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What complications result from chronically transfusing people?
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Iron overload!
-Multiorgan failure -CHF, liver cirrhosis Treatment: Iron chelators |
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What are some of the iron chelators used in this disease?
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Defroxamine
Deferasirox They're used for the beta thalassemias |
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What population is most commonly affected by sickle cell syndrome?
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African american population
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What mutation takes place in sickle cell anemia?
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V->E (valine-->glutamic acid) at 6th position of the beta globin gene
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What is the effect of the sickle cell mutation?
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Less soluble hemoglobin leads to precipitation of the Hgb-->sickling of the cells
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What is the effect of sickling on RBCs?
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Shorter lifespan
Infarction all over the body |
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What is the typical presentation of someone with sickle cell trait?
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It's asymptomatic.
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What is hemoglobin C?
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Similar disease to sickle cell, except that it's an E for K (glutamic acid for lysine) substitution at position 6
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What are thesymptoms of hemoglobincarriers?
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Anemia
Ulcers Splenomegaly |
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What are the different sickle cell diseases?
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Hg SS: homozygous S
Hg SC: heterozygous S, heterozygous C Hg S/B. thal disease: heterozygous S+B0/homozygous B+ |
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When do people present with sickle cell disease?
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As infants, when the Hgb F declines to less than 50%
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What are some types of sickle cell crises?
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Pain/vaso-occlusive crisis
Visceral sequestration crisis Aplastic anemia Hyperhemolytic crisis |
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What are some other kinds of problems that sickling blood cells can cause?
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Recurrent infections
Pulmonary HTN Renal failure |
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What are some infections that sickle cell people are more prone to?
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Parvovirus B19
Encapsulated bacteria: (strep, h. flu, meningococcus) |
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What are some of the vaso-occlusive crises that can happen with sickle cell disease?
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When there's vasoocclusion due to the sickling of blood cells inside the vasculature; normally pain
-Bones -Spleen -Stroke -Skin ulceration |
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What is the management for sickle cell pain crises?
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Pain meds
Correcting the precipitating factors: (dehydration,infection, etc.) |
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What is the treatment of people with sickle cell in relation to their increased number of infections?
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Prophylactic penicillin until 18
Immunizations |
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What is the treatment ofr an acute chest syndrome in a person with sickle cell disease?
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Blood exchange
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What's the treatment for sickle cell disease?
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Hydroxyurea: increases HbF; decreased HgS
Exchange transfusion (acute management) Pain management Blood transfusions |
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What are some of the reasons that people with sickle cell don't comply with meds?
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The side effects are quite severe.
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What is the cause of hereditary spherocytosis?
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Defect in vertical interactions:
-Spectrin -Protein 3 -Protein 4.2 Defect in Spectrin-Protein 4.2 binding |
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What is the cause of hereditary elliptocytosis?
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Defects in horizontal interactions:
-Protein 4.1 -Protein 3 -Glycoprotein C, D Defects in spectrin/spectrin-ankyrin binding |
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Who gets hereditary elliptocytosis more commonly?
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Africans/mediterraneans
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What problems happen in people with HS/HE?
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The RBCs get stuck in the spleen and then get destroyed
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What tests do you order up to diagnose hereditary elliptocytosis or spherocytosis?
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Negative Coomb's test
Abnormal osmotic fragility test Family history |
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What's the inheritance of Hereditary spherocytosis, elliptocytosis?
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Autosomal dominant
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What are the clinical findings of HS/HE?
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Anemia
Jaundice Chronic hemolysis Severe: -Splenomegaly -Gallstones |
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What are the treatments for HS/HE?
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If asymptomatic, don'ttreat
Folic acid supplementation Splenectomy (delay as long as possible.) |
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What are some of the immunizations that people with HS/HE should get? What meds should they be on?
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Immunizations:
-H. influenza -Meningococcus -P. pneumoniae Penicillin prophylaxis |
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What are the two most significant enzyme defects in RBCs?
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G6PD
Pyruvate kinase deficiency |
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What's the inheritance of G6PD?
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X-linked
Multiple mutations |
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What different variants of G6PD exist?
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African-American
Mediteranean Southeast asian |
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What is the function of G6PD?
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Maintain glutathione levels
Prevent free radical damage |
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What's the cause of RBC damage in people with pyruvate kinase deficiency?
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Decreased ATP-->rigid red cells-->hemolysis
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What's the inheritance of pyruvate kinase deficiency?
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Autosomal recessive
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What are the symptoms of pyruvate kinase deficiency?
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Hemolysis
Splenomegaly Neonatal jaundice |