Term
| Changes in chromatin, cell nucleus, reticulocytes, cytoplasm during Epoiesis |
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Definition
• Chromatin – more condensed as RBC matures: basophilic erythroblast poly- ortho-chromatophilic
• Cell Nucleus – becomes extruded to form reticulocyte (has some remaining RNA), matures to RBC
• Reticulocytes – this is precursor of RBC. Not normally seen in peripheral blood, if seen, may indicate early release of RBCs from marrow
• Cytoplasm – changes color from purple red as more hemoglobin produced |
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Term
EPO released where...due to....and causes?
What happens in chronic renal failure? |
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Definition
sensor for oxygen is produced in kidney in response to low hemoglobin & thus decreased O2 supply
• Effect – causes erythroid marrow hyperplasia, stimulates RBC production.
• Increased EPO – often a sign of a hemolytic process (sickle-cell, beta-thalassemia)
• Renal failure – causes low EPO chronic anemia; normally Hct is negatively related to EPO, in RF Hct declines b/c of lower EPO. |
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Term
| Hgb changes through development? |
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Definition
• Embryonic Hgb – ζ2ε2 tetramer, produced in yolk sac
• Hemoglobin F – has α2γ2 tetramer subunits, is fetal hemoglobin
• Hemoglobin A – has α2β2 tetramer subunits, is adult hemoglobin
• Hemoglobin A2 – has α2δ2 tetramer subunits, a sparser adult hemoglobin |
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Term
| Changes in O2 affinity with changes in pH, 2,3DPG, temp, CO2 |
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Definition
| Δ’d by pH (dumps O2 in acidic environment), 2,3 DPG (high altitude), and temperature |
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Term
| why fetal hgb has higher o2 affinity? |
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Definition
| binds less 2,3 DPG and thus has higher O2 affinity (left shift!) |
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Term
| T/R conformations of Hgb...affinity? |
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Definition
o “T” Tense State – nonaccepting, low O2 affinity (deoxygenated)
o “R” Relaxed State – accepting, high O2 affinity (partially oxygenated) binding cooperativity |
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Term
diff between hi/low affinity hgb variants
T/R, O2 delivery, DPG, |
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Definition
• High Affinity – favor “R” state, delivers less O2 to tissues, decreased affinity for 2,3 DPG, increased erythrocytosis, higher Hgb
• Low Affinity – favor “T” state, less likely to bind O2, delivers more O2 to tissues due to steric hindrance of heme; see cyanosis clinically, slate-gray color skin c/w cyanosis |
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Term
| Describe why hemolysis occurs with Heinz bodies |
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Definition
In Unstable hgb, you have increased suscepibility to oxidative stress, heme/globin complex is unstable Heinz bodies
o Heinz bodies – intracellular precipitates in RBCs that have weakened heme/globin binding
o Hemolysis – occurs when Heinz bodies bind to RBC membrane damages RBC, phagocytosis |
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Term
| Quiz: What does M Hgb cause? |
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Definition
| abnormal heme environment favoring “T” state right shifted curve, pseudocyanosis (brown-slate skin, no respiratory distress even though right shifted |
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Term
| rate limiting step of heme biosynthesis |
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Definition
| 1) Glycine + Succinyl CoA – makes aminolevulinate acid (ALA) in mitochondria; *rate-limiting* under negative feedback by heme |
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Term
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Definition
| in RBC => hemoglobin, but also in liver => “heme” enzymes (cytochrome P-450s, catalase) |
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Term
| after ALA is made in mitochondria what happens? |
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Definition
2) ALA leaves mitochrondria, enters cytosol, eventually converted to coproporphyringen III
3) Coproporphyringen III re-enters mitochondria, Fe incorporated into porphyrin ring by ferrochelatase => HEME! |
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Term
| what condition: X-linked lacks ALA synthase => can’t make ALA during heme biosynthesis => iron deposits around nucleus of erythroblasts (ringed sideroblasts) |
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Definition
sideroblastic anemia
iron deposits = (ringed sideroblasts) |
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Term
| Sx of overproduction of heme precursors due to lack of heme biosynth enzymes? |
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Definition
| Porphyria: increased excretion, photosensitivity, abd pain, neuro complications, sun-light induced rash. |
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Term
| proteins that give RBC a biconcave shape |
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Definition
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Term
| hereditary spherocytosis vs. elliptocytosis |
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Definition
• Hereditary spherocytosis – central pallor lost, phosphoplipid bilayer leaky, cell swells due to Band 3 or Ankyrin mutation
• Hereditary elliptocytosis – spectrin abnormal, RBC becomes elliptically shaped |
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Term
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Definition
• Na-K ATPase – sodium-potassium pump, key to maintain homeostasis in RBC, inhibited by ouabain
• Glycolysis – generates 2 ATP, also NADH/NADPH, moth balls and fava beans can alter metabolism resulting in hemolysis
• Pentose-Phosphate shunt – uses G6P to make NADPH synthesize glutathione (used by catalase) |
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Term
| process of degradation from beg to end? |
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Definition
• Senescent/Abnormal RBCs – degraded by RES reticulo-endothelial system (spleen 1o)
• Degradation – hemoglobin binds to haptoglobin, complex is then transported to liver:
o Globin Degradation – globin broken down into AAs
o Heme Degradation – broken down into Fe + biliverdin, which is reduced to bilirubin
o Fe Degradation – picked up by ferritin, can accumulate over time to make hemosiderin, iron overload results in hemosiderin deposits in other organs |
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Term
| What happens to Hgb unbound to haptoglobin? |
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Definition
• Hemoglobin Hemolysis – Hgb unbound to haptoglobin is oxidized to methemoglobin
o Met-heme – binds to albumin or hemopexin enters liver RES, heme catabolism
o Hemopexin – measure of hemolysis (like haptoglobin), low levels = high hemolysis, can be used to dx hemolytic conditions – indicates aggressive nature of disease! |
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Term
| Conj vs. Unconj bilirubin? |
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Definition
• Conjugated Bilirubin – esters added to bilirubin by bilirubin-UDP-glucuronyl transferase (BUGT)
o Water soluble – conjugated form very water soluble, can then be excreted
o Gilbert Syndrome, Crigler-Najjar Syndrome – BUGT mutated, hyperbilirubinemia
• Unconjugated Bilirubin – binds to albumin, less water soluble, elevated in jaundice
o Jaundice – from increased bilirubin load on immature liver, Tx by UV light |
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