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69 Cards in this Set
- Front
- Back
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What are the 3 basic mechanisms of anemia of inflammation?
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IL-1, TNF directly suppress erythroid colonies
Cytokines inhibit EPO secretion Hepcidin upregulation by IL-6 |
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What is the role of protease TMPR556 in hepcidin regulation?
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mediates hepcidin suppression in Fe deficiency
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What would transferrin and ferritin levels look like in anemia of inflammation vs. Fe deficiency?
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Transferrin will be normal/decreased in AI, but increased in Fe deficiency
Ferritin will be normal/increased in AI, but decreased in Fe deficiency (ferritin can be unreliable marker) |
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Role of the soluble transferrin receptor in diagnosis of anemia of inflammation vs. Fe deficiency?
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Increased in Fe deficiency (even with concomitant inflammation), usually normal in AI
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How do Vit D and EPO affect hepcidin regulation?
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Both decrease hepcidin
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What are all the protein components involved in hepcidin regulation?
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HFe (hemochromatosis gene), HJV, TfR2, and BMP-6/SMAD
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What is the bilayer coupling theory?
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minor abnormalities in lipid distribution translate into characteristically abnormal RBC shapes
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What are echinocytes and stomatocytes?
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Echinocytes: RBC with expanded outer layer
Stomatocytes: RBC with expanded inner layer |
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What is the role of Band 3 in the RBC membrane?
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Chloride/bicarb exchanger and binds membrane to cytoskeleton framework
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What are the roles of ankyrin and spectrin in the RBC membrane?
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Spectrin: supports bilayer and mediates motility of membrane proteins
ankyrin: associates spectrin to band 3 |
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What is the most common inherited hemolytic anemia?
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hereditary spherocytosis
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Pathophysiology of hereditary spherocytosis
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ankyrin dysfuction:
membrane fragmentation --> spherocytes increased splenic trapping --> hemolysis |
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Diagnosis of hereditary spherocytosis: labs and osmotic fragility test
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increased MCHC sign of spherocytosis, increased bili sign of hemolysis
osmotic fragility test: RBCs breakdown in more saline solution because of fragile membrane |
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Pathophysiology of hereditary elliptocytosis (hereditary pyropoikilocytosis more severe form)
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spectrin deficiency --> membrane instability ("cigar-shaped" RBCs)
HPP leads to membrane loss during fever |
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Pathophsyiology of Southeast Asian ovalocytosis
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band 3 deficiency--> membrane rigidity and decreased deformity --> mild anemia
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What are the inheritance patterns of the RBC "membranopathies"?
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Autosomal dominant
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What is the general problem in (hereditary) chronic non-spherocytic hemolytic anemia?
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deficiency in an enzyme in the PPP or glycolysis; importance of enzyme and function levels of mutant enzyme dictate severity of hemolysis
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Inheritance pattern and pathophysiology of glucose-6-phosphate dehydrogenase deficiency
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X-linked (female heterozygotes can have symptoms through lyonization pattern)
deficient PPP produces lack of reducing agents --> oxidation of Hgb which produces hemolysis |
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Pyruvate kinase deficiency pathophysiology (and why is the exercise tolerance test interesting for this anemia)?
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increased cation permeability leads to dehydration of RBCs and increased 2,3-DPG (which leads to ok oxygenation despite anemia)
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What is the Embden-Meyerhof pathway?
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glycolysis in RBCs
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Intravascular vs extravascular hemolysis
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Intravascular: mechanical damage mediated by complement via cold type Ab
Extravascular: macrophage mediated destruction via warm type Ab |
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Direct Coomb's Test
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Patient's RBCs with Abs/complement bound + anti-Ab's/anti-complement = agglutination
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Indirect Coomb's Test
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Patient's Abs + normal RBC's + anti-Abs = agglutination
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Pathophysiology of warm-antibody hemolytic anemia
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IgG's coat RBCs --> macrophages in spleen remove Abs with some membrane--> spherocytes and hemolysis
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Pathophysiology of drug-induced hemolytic anemia
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Antibodies bind to drug on RBC surface, bind to RBC surface and drug simultaneously (neoantigen), or drug induces anti-RBC antibody production
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pathophysiology of cold-antibody hemolytic anemia (often associated with infections)
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Complement-mediated hemolysis due to:
Anti-I IgM: Mycoplasma pneumoniae Anti-i IgM: lymphoma, mononucleosis |
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Expected results of Direct Coomb's test with cold agglutinin disease
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DAT is positive with anti-C3
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With which anemia are Donath-Landsteiner antibodies associated?
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Paroxysmal cold hemoglobinuria
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Hemolytic anemia associated with mechanical trauma to RBCs?
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Microangiopathic hemolytic anemia, e.g. HUS, DIC, TTP
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mutations in phosphatidyl-inositol-glycan A (PIG-A) is associated with which type of anemia?
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Paroxysmal nocturnal hemoglobinuria
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Pathophysiology of paroxysmal nocturnal hemoglobinuria
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defect in anchoring proteins in RBCs leads to fragmentation via complement, fragments trigger coagulation cascade, which leads to thrombosis
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Coomb's test with paroxysmal nocturnal hemoglobinuria?
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should be negative
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What causes spur cell anemia?
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excess cholesterol in RBC membranes as a result of liver disease
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How do you calculate the reticulocyte production index and what does the result indicate?
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(Rct%/2)x(pt Hct/normal Hct)
Above 2% indicates increased erythropoeisis |
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What is the significance of increased serum homocysteine?
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deficiency in folic acid or vitamin B12
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What is the significance of increased serum methylmalonate (MM CoA)?
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deficiency in B12
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What role do "R factors" have in B12 absorption?
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Produced by the salivary glands, binds B12, which is only liberated in more alkaline small intestine
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Where is the B12-intrinsic factor complex absorbed?
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ileum
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In a Schilling test positive for Pernicious anemia...?
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The first pass without IF added, little radioactivity appears in the urine (not absorbed) from radioactive B12, but during the second pass when IF is added, radioactivity appears in the urine
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What are the major mechanisms of pernicious anemia?
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loss of B12 absorption due to loss of intrinsic factor directly from Ab binding or Ab-mediated destruction of gastric parietal cells
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What are the two major clinical signs of B12 deficiency?
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Megaloblastosis
CNS problems, neuropathies |
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What is the result of folate deficiency during pregnancy?
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neural tube defects
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Is a nutritional deficiency more likely to contribute to B12 or folate deficiency?
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Folate deficiency
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Are there CNS/PNS signs associated with folate deficiency?
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Not really
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What is wrong with the serum folic acid test?
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It is very sensitive to recent intake and can be uninformative even after one meal in the hospital
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What major Hgb chains appear on chromosome 11?
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Embryonic (epsilon), fetal (gamma), delta, and beta
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What major Hgb chains appear on chromosome 6?
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Embryonic (zeta), alpha
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What genetic region is responsible for hemoglobin switching?
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the locus control region
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By 10 weeks, which is the predominant Hb?
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HbF --> alpha2/gamma2
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By 6 months after birth, which is the predominant Hb?
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HbA --> alpha2/beta2
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Why is SCD considered a balanced polymorphism?
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Heterozygotes get protection from malaria
Homozygotes have increased morbidity/mortality |
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What is the major mutation responsible for SCD?
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GAG (glutamic acid) --> GTG (valine) in the beta globin chain
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In SCD, what is a compound heterozygote?
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Both alleles are abnormal, with a HbS and an HbC or absent/reduced HbB expression (the later two form sickling syndrome)
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Under what conditions do the HbS globin subunits polymerize in SCD?
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Deoxygenation state (reversible)
Dehydration state (irreversible) disruption in cation homeostasis due to drop in pH, sickling, or increase in Ca2+ |
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What causes vaso-occlusion in SCD? (5 things)
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increased RBC adhesion
platelet activation damage to endothelium oxidative stress from reperfusion injury Free Hb acts as sink for NO |
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What is the role of hydroxyurea in the treatment of SCD?
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increases HbF, which decreases polymerization of HbS
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What is HbE disease?
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A compound heterozygote with HbE/HbB(o or +) results in severe thalaseemia (HbE/HbE is benign)
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What is thalassemia major?
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any thalassemia patient that requires 8 or more transfusions/year
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What is thalassemia intermedia?
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any thalassemia patient that requires 7 or fewer transfusion/year
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What is thalassemia minor?
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anyone with a heterozygous beta globin mutation
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What are alpha thalassemia-1 and 2?
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alpha thal-2: silent trait, 3 functional Hb alphas
alpha thal-1: severe trait, normal-mild anemia, 2 functional Hb alphas |
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What is HbH disease? Why are there polka-dot RBCs?
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Having only 1 functional Hb alpha, which leads to moderate anemia, splenomegaly, and colelithiasis
HbH is tetramers of beta globin, which precipitate forming polka-dots |
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What is the difference between HbH disease and HbH + Hb constant spring?
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HbH = 1 Hb alpha
HbH +HbCS = 1 Hb alpha + 1 HbCS, which produces a more severe anemia than HbH alone with hepatosplenomegaly |
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What is the thalassemia-associated cause of hydrops fetalis?
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no functional Hb alpha genes
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What is Hb Bart, and why does it appear in HbH disease?
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Hb Bart is a gamma globin tetramer that forms due to the gamma globin numbers exceeding alpha globin numbers in HbH disease
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Why are free alpha globins a problem in beta thalassemia?
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alpha globin chains attach to and destroy the RBC membrane before maturity
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Describe the chain of events that occurs causing the symptoms of beta thalassemia
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RBCs get destroyed before leaving the marrow, causing anemia (ineffective erythropoiesis)
anemia-->EPO secretion-->Fe overload and bone marrow expansion surviving RBCs are sequestered in the spleen-->hypersplenism |
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What is a cause of hepatosplenomegaly in severe beta thalassemia?
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extra-medullary hematopoiesis
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What are 3 major differences in the presentation of alpha thalassemia vs. beta thalassemia
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HbBart (gamma tetramers)-->disappears soon after birth
HbH (beta tetramers) more hemolysis because more cells enter circulation |
