hema 1 lec

• Erythrocytes


  Red blood cells
• Red blood cell


  • Size: 7-8 um, average 7.2 um
  • Shape: Biconcave Disc
  • Lifespan: 90-120 Days
  • Function: Efficient transport of oxygen from the lungs to the tissues, and carbon dioxide from the tissues to the lungs

  
• Methemoglobin

  Ferric state of blood, chocolate brown
• Carboxyhemoglobin


  Bound to carbon monoxide which has 210 times greater affinity, cherry red
• Sulfhemoglobin


  Exposure to sulfhydryl compounds, mauve-lavender/irreversible
• Red blood cell membrane

  • Separates the intracellular fluid environment from the extracellular fluid environment
  • Allows nutrient and ion passage selectively in and out of the cell
  • Allows the cell to deform when required
• Composition of red blood cell membrane

  • 52% Proteins
  • 40% Lipids (Phospholipids, Cholesterol)
  • 8% Carbohydrates
• Spectrin


  Cytoskeletal protein, very important, interacts with other proteins like Ankyrin
• Ankyrin


  Bound to Band 3 protein
• Band 3


  Anion exchanger, allows anions like chloride, phosphate, bicarbonate to pass through
• Band 4.2


  Stabilizes the linkage of ankyrin to band 3
• Glycophorin C


  Transmembrane protein, gives RBC a negatively charged surface, contains sialic acid
• Protein interactions in the red blood cell membrane are important, as one absence of a protein will incur damages to the system
• Hereditary spherocytosis


  Problem in the spectrin protein, red blood cells become spherical instead of biconcave, tend to hemolyze leading to anemia
• Examples of transporter membrane proteins and functions


  • Aquaporin 1 - Water transporter
  • Band 3 - Anion exchanger 1, anion transporter, support system for surface antigens of ABO blood group antigens
  • Duffy blood group antigens - Ca2+ transporter
  • GLUT1 - Glucose transporter, supports ABO blood group antigens
  • Glycophorin A - Transports negatively charged sialic acid, supports MN blood group antigens
  • Glycophorin B - Transports negatively charged sialic acid, supports Ss blood group antigens
  • Glycophorin C - Transports negatively charged sialic acid, supports Gerbich blood group system antigens
  • ICAM 4 - Integrin Adhesion
  • Kell blood group antigens - Zn2+ binding endopeptidase, supports Kell blood group antigens
  • Kidd blood group antigens - Urea transporter
  • Rh blood group antigens - Supports D and CcEe blood group antigens
  • Rh antigen expression protein - Supports DCcEe antigen expression, gas transporter (probably CO2)

  
• Ionic transport and hydration homeostasis

  1. Passive leak through ion channels driven by electrochemical gradients

  2. Gradient-driven passive or secondary active transporters like Band 3, KCC, NKCC, KNHE

  3. PIEZO1

  4. Gardos

  5. Active exchange through Na+/K+ pump and Ca2+ pump
• Calcium-ATPase is regulated to prevent accumulation of calcium, as calcium causes mineralization which makes the red blood cell membrane rigid and difficult to pass through the spleen
• Red blood cell cytoplasm

  • Accurate balance of intracellular K+, Na+ and Ca2+
  • Glucose, intermediate products of glycolysis
  • Glycolytic enzymes
• Characteristics of red blood cells

  • Anucleated - no nucleus
  • Organelles are extruded out during maturation
  • Limited metabolic activity - anaerobic respiration
  • Perform red blood cell functions efficiently
  • Maintain red blood cell membrane integrity
  • Maintain intracellular electrolyte balance
  • Live the entire lifespan of red blood cells
• Glycolysis pathway - Embden Meyerhof pathway

  1. Glucose is the most immediate source of energy

  2. Insulin allows glucose entry into the cell

  3. 2 ATP are consumed, 4 ATP are produced per molecule of glucose

  4. Produces 90% of glucose energy used by red blood cells

  
• Hexose-monophosphate pathway


  Also known as pentose phosphate pathway, protects hemoglobin from oxidative stress by generating NADPH

  
• Glucose-6-phosphate dehydrogenase (G6PD)


  Converts glucose-6-phosphate to 6-phosphogluconate, producing NADPH in the process

  
• Normal G6PD activity can detoxify oxidative compounds and safeguard hemoglobin, sulfhydryl-containing enzymes and membrane thiols, allowing normally functioning red blood cells to carry large quantities of oxygen safely

  
• G6PD deficiency


  Exposure of hemoglobin to oxidation leading to the precipitation of hemoglobin as Heinz bodies

  
• Heinz bodies


  Precipitated hemoglobin, appear as dots near the periphery of the red blood cell, make the cell less flexible and deformable

  
• Methemoglobin reductase pathway


  Prevents oxidation of iron, maintains iron in ferrous (Fe2+) state within hemoglobin
• Methemoglobin


  Oxidized form of hemoglobin with ferric (Fe3+) iron, impairs oxygen delivery

  
• Luebering-Rapoport pathway


  1. Regulates oxygen release in the tissues

  2. Generates 2,3-diphosphoglycerate (2,3-DPG)

  3. 2,3-DPG binds to hemoglobin, decreasing its affinity for oxygen and allowing more oxygen to be released in the tissues

  
• Hypoxia (decreased oxygen tension in tissues)


  Increases the level of 2,3-DPG and decreases pH, which further decreases hemoglobin's affinity for oxygen, allowing more oxygen to be released in the tissues

  
• 2,3-DPG


  A SALT BRIDGE that forms between the 2 BETA CHAIN
• 2,3-BPG is more abundant in the TISSUES


  Because this is where deloading of oxygen occurs

  
• When there is an increased need for oxygen


  There will also be rapid production of 2,3 BPG

  
• What happens when there is Hypoxia?

  1. Hypoxia occurs when there is decreased oxygen tension into the tissues

  2. RBC must deliver more oxygen at a faster rate to compensate

  3. There will be a decrease in hemoglobin affinity which allows more oxygen to be released in tissues

  4. It also drives glycolysis to increase → more ATP → more 2,3-GDP generated and a drop in pH

  5. An acid environment causes a decrease in the oxygen-hemoglobin affinity → increase in the release of oxygen into the tissues

  
• Mechanism of hypoxia


  • Increase the level of 2,3-GDP
  • Decrease in pH
• 2,3-GDP becomes saturated and bounds to the hemoglobin

  
• Fully saturated 2,3-GDP will increase the rate of glycolysis
• Senescence


  The RBC already served its entire lifespan; NORMAL LIFESPAN OF RBC: 90-120 Days
• Hemolysis


  A normal process when aged RBCs are being destroyed, some parts of the cell are being recycled
• Destruction of RBCs


  • As the cells reach senescence (old age), mature RBCs are no longer capable of replenishing needed enzymes and proteins because primarily it is a ANUCLEATED cell
  • Deterioration in these elements will eventually lead to erythrocyte death, and thus destruction
• Eryptosis


  The death of RBCs in the spleen, a form of apoptosis precipitated by factors such as oxidative stress, energy depletion, and membrane signals that stimulate phagocytosis