Download MLAB 1415: Hematology Keri Brophy-Martinez Erythrocytes: Part Two

MLAB 1415: Hematology
Keri Brophy-Martinez
Erythrocytes:
Part Two
Red Blood Cell Membrane
• Structure
▫ Trilaminar, threedimensional
 Outermost layer:
glycolipids,
glycoproteins
 Central layer:
cholesterol,
phospholipids
 Inner layer:
cytoskeleton
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
Red Blood Cell Membrane
• Function
▫ Shape
 Provides the optimum surface to volume ratio for respiratory exchange
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
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
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
Glycolysis or
Embden-Meyerhof Pathway
 Generates 90- 95% of energy needed by
RBC’s
 Glucose is metabolized and generates
two molecules of ATP (energy).
 Functions in the maintenance of RBC
shape, flexibility and the cation pumps
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
can’t be neutralized and globin denatures then
precipitates. The precipitates are referred to as
Heinz bodies




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.
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
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
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 RBC’s or senescent RBC’s 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 RBC’s.
Erythrocyte Destruction
• Two Paths
▫ Extravascular
▫ Intravascular
Extravascular Destruction
• Hostile surrounding in the spleen, stress the
RBC
• Glycolysis slows, ATP production ends
• Intracellular sodium increases, potassium
decreases
• Water ends the cell- RBCs loose flexibility
• RBC’s are now trapped in spleen
Extravascular Destruction
• The RES cells lyse the RBC’s and digest them. Components of the RBC are
recycled.
▫ Iron is transported by transferrin to the bone marrow to be
recycled into hemoglobin or stored in the macrophage
▫ 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 (direct) and unconjugated (indirect) bilirubin can be
used to monitor hemolysis.
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.
Intravascular Destruction
▫ The free hemoglobin α and β 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).
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.
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.