MLAB 1415: Hematology Keri Brophy-Martinez

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MLAB 1415 HematologyKeri Brophy-Martinez

• Chapter 5 Erythrocytes
• Part Two

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Red Blood Cell Membrane

• Structure
• Trilaminar, three-dimensional
• Outermost layer glycolipids, glycoproteins
• Central layer cholesterol, phospholipids
• Inner layer cytoskeleton

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Cytoskeleton of the RBC Membrane

• Components
• Spectrin
• Composed of alpha beta chains
• Join to form a matrix which strengthens the
  membrane against sheer force and controls
  biconcave shape
• Ankyrin
• Binding site for spectrin

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Red Blood Cell Membrane

• Function
• Shape
• Provides the optimum surface to volume ratio for
  respiratory exchange AND is essential to
  deformability
• Provide deformability, elasticity
• Allows for passage through microvessels
• Provides permeability
• Allows water and electrolytes to exchange via
  cation pumps
• RBC controls volume and H2O content primarily
  through control of sodium and potassium content

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Metabolic Pathways

• Metabolism
• Limited
• Energy required for
• Maintenance of cation pumps
• Maintenance of hgb in reduced state
• Maintenance of reduced sulfhydryl groups in hgb
  and other proteins
• Maintenance of RBC integrity and deformability

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Key Metabolic Pathways for the Erythrocyte

• Glycolysis or Embden-Meyerhof pathway
• Hexose Monophosphate Shunt
• Methemoglobin reductase pathway
• Rapoport- Luebering Shunt
• Key actions
• Use enzymes to supply energy for the system
• Reduce oxidants in the system

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Glycolysis or Embden-Meyerhof Pathway

• Generates 90- 95 of energy needed by RBCs
• Glucose is metabolized and generates two
  molecules of ATP (energy).
• Functions in the maintenance of RBC shape,
  flexibility and the cation pumps

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Hexose monophosphate shunt

• Metabolizes 5-10 of glucose.
• NADPH is end product
• Protects the RBC from oxidative injury.
• Most common defect is deficiency of the enzyme
  glucose-6-phosphate dehydrogenase (G-6PD).
• If the pathway is deficient, intracellular
  oxidants cant be neutralized and globin
  denatures then precipitates. The precipitates
  are referred to as Heinz bodies

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Methemoglobin Reductase pathway

• Maintains iron in the ferrous (Fe) state.
• In the absence of the enzyme (methemoglobin
  reductase), methemoglobin accumulates and it
  cannot carry oxygen.

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Rapoport Leubering Shunt

• Allows the RBC to regulate oxygen transport
  during conditions of hypoxia or acid-base
  imbalance.
• Permits the accumulation of 2,3-DPG which is
  essential for maintaining normal oxygen tension,
  regulating hemoglobin affinity

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Red Blood Cell Metabolism Summary

• Three areas of RBC metabolism are crucial for RBC
  survival and function.
• RBC membrane
• Hemoglobin structure and function
• RBC metabolic pathways cellular energy

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Erythrocyte Destruction

• Breakdown of the RBC
• Toward the end of 120 day life span of the RBC,
  it begins to break down.
• The membrane becomes less flexible.
• The concentration of cellular hemoglobin
  increases.
• Enzyme activity, especially glycolysis,
  diminishes
• Removal
• Aging RBCs or senescent RBCs are removed from
  the circulation by the reticuloendothelial system
  (RES) which is a system of fixed macrophages.
  These cells are located all over the body, but
  those in the spleen are the most efficient at
  removing old RBCs.

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Erythrocyte Destruction

• Two Paths
• Extravascular
• Intravascular

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Extravascular Destruction

• The RES cells lyse the RBCs and digest them.
  Components of the RBC are recycled.
• Iron is transported by transferrin to the bone
  marrow to be recycled into hemoglobin.
• Amino acids from globin are recycled into new
  globin chains.
• The protoporphyrin ring from heme is broken and
  converted into biliverdin
• Biliverdin is converted to unconjugated bilirubin
  and carried to the liver by albumin, a plasma
  protein.
• Bilirubin is conjugated in the liver and excreted
  into the intestine, where intestinal flora
  convert it to urobilinogen.
• Most urobilinogen is excreted in the stool, but
  some is picked up by the blood and excreted in
  the urine.
• Conjugated (indirect) and unconjugated (direct)
  bilirubin can be used to monitor hemolysis.

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FIGURE 5-6 Most hemoglobin degradation occurs
within the macrophages of the spleen. The globin
and iron portions are conserved and reutilized.
Heme is reduced to bilirubin, eventually degraded
to urobilinogen, and excreted in the feces. Thus,
indirect indicators of erythrocyte destruction
include the blood bilirubin level and
urobilinogen concentration in the urine.
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Intravascular Destruction

• The free hemoglobin a and ß dimers that are
  released into the bloodstream is picked up by a
  protein carrier called haptoglobin.
• The haptoglobin-hemoglobin complex is large and
  cannot be excreted in the urine. It is carried
  to the liver where the RES cells are and the
  breakdown process occurs as in extravascular
  destruction.
• If there is an increase in intravascular
  destruction, the haptoglobin is used up and free
  hemoglobin is excreted in the urine
  (hemoglobinuria).

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FIGURE 5-7 When the erythrocyte is destroyed
within the vascular system, hemoglobin is
released directly into the blood. Normally, the
free hemoglobin quickly complexes with
haptoglobin, and the complex is degraded in the
liver. In severe hemolytic states, haptoglobin
can become depleted, and free hemoglobin dimers
are filtered by the kidney. Additionally, with
haptoglobin depletion, some hemoglobin is quickly
oxidized to methemoglobin and bound to either
hemopexin or albumin for eventual degradation in
the liver.
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References

• Diggs, L., Strum, D., Bell, A. (1975). The
  Morphology of Human Blood Cells. North Chicago
  Abbott laboratories.
• http//tiny.cc/lwgtg
• McKenzie, S. B., Williams, J. L. (2010).
  Clinical Laboratory Hematology . Upper Saddle
  River Pearson Education, Inc.