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76 Cards in this Set
- Front
- Back
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How can B-thalassemia, or any anemia, lead to somatic pain?
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anemia = low oxygen = stimulate reticulocytes = increase in bone marrow mass = impinge nearby structures
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A patient with hereditary spherocytosis has gallstones. What is the primary compound forming these gallstones?
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unconjugated bilirubin from excess hemolysis in the spleen
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What are the granulocytes?
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neutrophils, eosinophils, basophils
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In H/E, neutrophils stain what color?
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pink
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In H/E, eosinophils stain what color?
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red
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In H/E, basophils stain what color?
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blue
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What is a respiratory burst?
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increase in production of reactive oxygen species for phagocytosis; neutrophils initiate this
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What type of granulocytes initiate a "respiratory burst"?
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neutrophils
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What are the types of lymphocytes?
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T, B, NK cells
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Where are T cells made?
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bone marrow (mature in thymus)
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The term hypochromic refers to ...
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low hemoglobin levels
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The term microcytic refers to ...
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low volume RBCs (low MCV)
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An RBC with defective DNA synthesis will lead to what type of RBC? (size and hemoglobin content)
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macrocytic, normochromic (like B12 deficiency)
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An RBC with defective hemoglobin synthesis will lead to what type of RBC? (size and hemoglobin content)
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microcytic, hypochromic
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Hemolytic anemias will lead to what type of RBC? (size and hemoglobin content)
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normocytic, normochromic (cells are proper, but destroyed easily)
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What method is used to count cells reported in the CBC?
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flow cytometry
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How do RBCs create ATP?
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glycolysis only (they have no mitochondria)
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What is the Rapaport-Luebering Shunt in a RBC?
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During glycolysis, RBCs can shift from ATP production to BPG production.
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In hemoglobin, what state does iron need to be in to bind oxygen? (2+ ferrous or 3+ feric)
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ferrous can bind oxygen
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A defect in Glucose 6 phosphate dehydrogenase (G6PD) can lead to anemia. How?
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G6PD decreases = accumulation of oxidative species in the RBC during glycolysis = hemolysis = hemolytic anemia
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Why does a decrease in pyruvate kinase lead to anemia?
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pyruvate kinase defect = low glycolysis = low ATP = low membrane protein function = cell water loss = rigid cell = damage in the spleen cords
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Increased levels of BPG are seen in response to what condition?
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hypoxia. BPG decreases hemoglobin affinity for oxygen in tissue = more oxygen released to tissue
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Why do patients with methemoglobin (HbM) appear cyanotic?
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HbM stabilizes the ferric state of hemoglobin bound to oxygen so oxygen is not released to tissues; it is blue colored
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Patients with hemolytic anemias are more resistant to what disease?
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malaria
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Why do patients with a B6 deficiency exhibit microcytic, hypochromic RBCs?
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B6 is needed for heme synthesis. anemia due to low Hb synthesis = low MCV/MCH = microcytic, hypochromic
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In heme synthesis, Succinyl CoA + glycine =
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ALA, uses ALA synthase enzyme
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In heme synthesis, 2 molecules of ALA condense to form ...
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Pyrrole
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How does lead poisoning lead to death?
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lead blocks ALA dehyratase. protoporphyrin IX accumulates and heme synthesis decreases
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Why does iron need to be bound to carrier proteins in plasma?(apotransferrin)
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free iron is toxic
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Apotransferrin + iron =
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transferrin
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Why do porphyrias lead to skin damage?
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Porphyrias are defects in heme biosynthesis pathway. accumulation of intermediates leads to reactive oxygen species
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Iron is stored by being bound to what molecules?
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apoferritin or hemosiderin (if excess is present)
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How does heme regulate its own production? What enzyme is inhibited by Heme?
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ALA synthase production is inhibited by heme accumulation creating a negative feedback loop; also heme works as an allosteric modifier of the enzyme
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Unsoluble/unconjugated bilirubin is combined with what compound to become soluble?
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glucaronic acid is added in the liver during conjugation
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Unconjugated bilirubin is insoluble. How does it get from the spleen to the liver?
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bound to carrier protein (albumin)
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Why are women more likely to be anemic than men?
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menstruation = iron/RBC loss; also during pregnancy, they must supply enough iron for growing fetus also
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Conjugated bilirubin enters the bile and then the intestines. How does it get into the feces?
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intestinal bacteria deconjugate bilirubin and create urobilinogens, urobilins (e.g. stercobilin)
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Why would we expect high levels of ALA synthase activity after treating a patient with a phenobarbital?
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phenobarbital induces cytochrome p450 enzyme formation so it can degrade it = heme is being used to create this enzyme = less heme for hemoglobin = ALA synthase will start the pathway to make more heme
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Where are non-deformable RBCs filtered out of circulation?
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spleen trabeculae
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Major cytoskeletal proteins found on the cytoplasmic side of an RBC that allow for high deformability?
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spectrin, actin, ankyrin, band 4.1, band 4.2
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Defects in RBC cytoskeletal protein will lead to what type of anemia?
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hemolytic, the cells are less deformable in the spleen and small capillaries
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Spectrin is connected to the plasma membrane by what protein?
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ankyrin
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When RBCs are under much stress, their shape changes. What happens to their surface area?
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always remains constant due to spectrin's constant reforming
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An increase in H+ concentration has what affect on oxygen binding to hemoglobin?
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high H+ = low pH = shift curve right = oxygen dissociates easier into tissue
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How does BPG facilitate oxygen release into tissues?
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BPG binds in the hemoglobin binding pocket = conformational change releasing oxygen
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What is the Bohr Effect?
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HbH+ (protonated hemoglobin) releases oxygen easier to tissues (shift to the right of the binding curve)
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How does most CO2 get to the lungs from tissue? bicarbonate or bound to hemoglobin?
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bicarbonate (only a small portion is bound to hemoglobin)
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How does high CO2 cause a shift to the right on the hemoglobin binding curve (easier release into tissues)?
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CO2 bound to hemoglobin stabilizes the deoxy state (so less O2 bound to hemoglobin = more into tissue)
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Most hematopoietic growth factors bind to what type of receptors?
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receptors that recruit tyrosine kinase (JAK/STAT pathway)
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What does dimerized, activated STAT do to convey a growth factor signal?
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enters the nucleus to act as a transcription factor
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What effect does SOCS have on the hematopoietic proliferation?
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inhibits it by reducing the JAK/STAT pathway
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What is leukemia?
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malignancies of the blood. hematopoietic cells remain in a proliferative state
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What is SCID (severe combined immunodeficiency disease)?
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no T cells, inactive B cells. due to bad IL-2 receptor. no JAK/STAT pathway
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How does SHP-1 inhibit hematopoiesis?
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dephosphorylates JAK2 (no JAK/STAT pathway)
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Why might a patient with a defective erythropoietin receptor that cannot bind SHP-1 have leukemia?
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if the receptor cannot bind SHP-1, JAK/STAT is constantly activated. SHP-1 inactivates JAK. RBCs are constantly being made
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How do SOCS inhibit the JAK/STAT pathway?
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inhibit JAK
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How do PIAS inhibit the JAK/STAT pathway?
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inhibit/degrade/prevent dimerization of STAT
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Do reticulocytes have a nucleus?
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no, but some other organelles are still seen
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Where do reticulocytes mature?
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spleen
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Iron deficiency leads to RBCs that look ...
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microcytic/hypochromic, bad heme synthesis
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RBCs with B12/folate deficit look ...
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megaloblastic, bad DNA synthesis
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Sickle cell anemia (HbS) is a change in the HbB chain from glutamate to ______
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valine
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HbC results from a change of glutamate to _____
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lysine
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How can Sickle cell anemia can lead to gallstones?
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excess hemolysis in spleen = high unconjugated bilirubin = liver cannot process it = high unsoluble bilirubin precipitates in bladder= gallstones
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What is thalassemia?
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hemoglobin chain (A and B) are not made in equal proportion= lower hemoglobin concentrations= anemia
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Which thalassemia is more serious (A or B)?
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B. low B chains = high A chains= no stable Hb tetramers are formed
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Why does HbF have a greater affinity for oxygen?
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instead of B chain, HbF has a gamma chain = decreased affinity for BPG = more oxygen stays bound to the heme (BPG stabilizes the deoxy state)
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How do patients with a-thalassemia develop anemia?
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a-thalassemia = more B chains = HbH forms= high oxygen affinity = no oxygen to tissue
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What is the difference between HbF and HbA?
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HbA is normal 2 alpha and 2 beta chains; HbF has 2 alpha chains ans 2 gamma chains. HbF has a higher oxygen affinity
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What is hemoglobin "switching"?
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shifting production of HbF to HbA; seen in growing infants
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Why does research want to elevate levels of HbF in patients with hemoglobinopathies?
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most hemoglobinopathies are caused by Beta chain defects; HbF uses gamma chains instead of beta chains so, while not ideal, the RBCs may be able to regain some normal function
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Elevated levels of HbF would be most helpful to a patient with what type of thalassemia? A or B?
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patients with B thalassemia have defective B chain synthesis. HbF contains no beta chains so it could be made properly. If a patient had A thalassemia, they would have defective alpha chain synthesis and HbF would also be defective
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How do deletion mutations of HPFH (hereditary persistance of Fetal hemoglobin) cause high HbF levels?
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point mutation is in the gamma chain promoter. more production of gamma chains = higher HbF
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How can a deletion mutation causing persistence of fetal hemoglobin help patients with B thalassemia?
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deletion of the B chain genes = only HbF can be made = some oxygen binding can occur better than if we had totally defective B chains
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Where does erythropoiesis occur at 6 weeks gestation?
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liver (some spleen)
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During gestation, where are RBCs first made before 6 weeks?
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yolk sac
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