red cell metab

Question 1

Maturation and senescence of RBC

Answer 1

• Erythrocytes lose nuclei before entering circulation
• mRNA disappears 1-2 days after release
• there is no protein synthesis (no replacement of damaged molecules)
• cytokeleton and membranes degenerate, cells lose elasticity

Question 2

End of RBC life

Answer 2

• Old, Inelastic RBC are trapped in the spleen and phagocytosed by macrophages (macrophages break RBC down completely)
  
  • extravascular hemolysis (no RBC lysis in vasculature)
• Correlation: defects in cytoskeleton shorten RBC lifespan
  
  • HEREDITARY SPHEROCYTOSIS = SPECTRIN mutation leads to ROUNDED, short lived cells

Question 3

INtravascular Hemolysis vs extravascular hemolysis (spleen)

Answer 3

• Intravascular hemolysis
  
  • mechanical disruption
  • release of hemogloin from RBC
  • Hemoglobinuria
• Extravascular hemolysis (spleen) (normal)
  
  • removal of STIFF RBCs
  • release of bilirubin from RBCs
  • Possible jaundice

Question 4

Purpose of RBC metabolism

Answer 4

• Keeping Iron reduced (Fe2+)
  
  • NADH
• Maintaining K+/Ca2+ gradients
  
  • ATP
• Keeping protein SH-group reduced
  
  • NADPH
• Maintaing cell shape (keeps cytokeletal working)
  
  • ATP

IF RBC METABOLISM FAILS

• CELLS FILL WITH Ca2+, Cells release K+, LOSE BICONCAVE SHAPE

Question 5

RBC glycolysis and PPP

Answer 5

Question 6

Glycolysis in RBC

Answer 6

• REgulated Steps:
  
  • Hexokinase
  • Phosphofructokinase
• NOT RESPONSIVE TO INSULIN (cannot switch to alternate energy source)
• Responsive to pH
  
  • Acidic pH INHIBITS GLYCOLYSIS
    
    • LESS lactate production

Question 7

role of 2,3 Bisphosphoglycerate molecule

Answer 7

• 1,3 cisphosphoglycerate (1,3 BPG) can be converted into 2,3 BPG
  
  • 2,3 BPG can re-enter glycolysis by dephosphorylation to 3-phosphoglycerate. NO ATP, JUST NADH gain from glycolysis (ATP NEUTRAL)
• 2,3 BPG synthesis is inhibited at LOW pH
  
  • Less glycolysis, less 2,3 BP production
  • ACIDOSIS reduces 2,3 BPG concentration and improves oxygen saturation
    
    • improves affinity of oxygen to hemoglobulin

Question 8

Describe Pentose Phosphate Pathway

Answer 8

• PPP is to provide REDUCTION EQUIVALENTS in the form of NADPH
• Low intracellular NADPH concentration activates glucose 6-phophsate dehydrogenase
• Pentose products are RE-introduced into glycolysis

Question 9

importance of Glutathione

Answer 9

• ROS oxidize protein sulfhydryl groups
  
  • structural proteins and enzymes denature
  • GSH keeps sulfhydryl groups reduced
• Superoxide radical O2- is converted to H2O2 by superoxide dismutase
  
  • GSH provides electrons to convert H2O2 to H20

Question 10

Cytoskeletal problems vs enzymatic problems

Answer 10

• cytoskeletal problems can cause SPHEROCYTIC ANEMIA
• ENZYMATIC PROBLEMS can cause NONSPHEROCYTIC ANEMIA
  
  • G6PD deficiency causes hemolytic anemia for lack of NADPH
  • Pyruvate kinase dificiency causes hemolytic anemia for lack of NADH/ATP

Question 11

Glucose 6-phosphate dehydrogenase (PPP defect)

Answer 11

• X-linked recessive
• prevalent in african/mediterranena populations
• HEMOLYTIC CRISES TRIGGERED BY:
  
  • infection, H2O2 producing drugs, FAVA beans
• leads to SPLENOMEGALY, JAUNDICE
• Forms Heinz body –> cleaved by macrophages (looks like they took a bite out of it)

Question 12

Pyruvate kinase deficiency (glycolysis defect)

Answer 12

• Rare
• Hereditary, non-spherocytic hemolytic anemia
• crisis not triggered by ROS
  
  • NADH/ATP
• Splenomegaly jaundice
• characteristiclly Blebbing of the RBC which leads to collapse

Question 13

Metabolism of cancer cells

Answer 13

• Tumor cells get energy from glycolysis
  
  • produce large amounts of LACTATE
• Tumor cells operate under HYPOXIC CONDITIONS
  
  • expression hypoxia-inducible factor 1-alpha (HIF-1alpha) to support anaerobic metabolism

Question 14

RBC cytoskeletal defect

Answer 14

• present as hereditary spherocytosis
• autosomal dominant
• most common = Ankyrin mutation