MLAB 1415: HematologyKeri Brophy-Martinez

Chapter 5: ErythrocytesPart Two

Red Blood Cell Membrane• Structure

▫ Trilaminar, three-dimensional

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 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

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• 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.▫ 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.

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.