Red Blood Cell Membrane Development And Function

The mature red blood cell is a magnificently designed instrument for hemoglobin delivery. As a hemoglobin-filled sac, the red cell travels more than 300 miles through the peripheral circulation, submitting itself to the swift waters of the circulatory system, squeezing itself through the threadlike splenic sinuses, and bathing itself in the plasma microenvironment. Cellular and environmental factors contribute to red cell survival. In order for the red cell to survive for its 120-day life cycle, these conditions are necessary:

• The red cell membrane must be deformable.

• Hemoglobin structure and function must be adequate.

• The red cell must maintain osmotic balance and permeability.

The mature red blood cell is an anucleate structure with no capacity to synthesize protein, yet it is capable of a limited metabolism, which enables it to survive 120 days.3 An intact, competent, and fully functioning red cell membrane is an essential ingredient to a successful red cell life span. The membrane of the red cell is a trilaminar and three-dimensional structure containing glycolipids and glycoproteins on the outermost layer directly beneath the red cell membrane surface. Cholesterol and phospholipids form the central layer, and the inner layer, the cytoskeleton, contains the specific membrane protein, spectrin, and ankyrin (Fig. 3.8).

Composition of Lipids in the Interior and Exterior Layers

Fifty percent of the red cell membrane is protein, while 40% is lipid and the remaining 10% is cholesterol. The lipid fraction is a two-dimensional interactive fluid that serves as a barrier to most water-soluble molecules. Cholesterol is equally distributed through the red cell membrane and comprises 25% of the membrane lipid; however, plasma cholesterol and membrane cholesterol are in constant exchange. Cholesterol may accumulate

Membrane surface

Lipid bilayer

Membrane surface

Lipid bilayer

Membrane - cytoskeleton

"t

Spectrin dimer-dimer interaction

Adducin

Protein

Spectrin

Figure 3.8 Red blood cell membrane. Note placement of integral proteins (glycophorins—in purple) versus peripheral proteins (spectrin, ankyrin).

Membrane - cytoskeleton

"t

Spectrin dimer-dimer interaction

Adducin

Protein

Spectrin

Figure 3.8 Red blood cell membrane. Note placement of integral proteins (glycophorins—in purple) versus peripheral proteins (spectrin, ankyrin).

38 Part I • Basic Hematology Principles on the surface of the red cell membrane in response to excessive accumulation in the plasma. Increased plasma cholesterol causes increased deposition of cholesterol on the red cell surface. The red cell becomes heavier and thicker, causing rearrangement of hemoglobin. This may be one pathway to the formation of target cells and acanthocytes, red cell morphologies that exhibit decreased red cell survival. Acanthocytes may also develop subsequent to cholesterol depositions in patients with liver disease and lecithin cholesterol acetyltransferase (LCAT) deficiency.

Composition of Proteins in the Lipid Bilayers

The protein matrix of the red cell membrane is supported by two types of protein. The integral proteins start from the cytoskeleton and expand through the membrane to penetrate the other edge of the red cell surface. Peripheral proteins are confined to the red cell cytoskeleton. The integral proteins provide the backbone for the active and passive transport of the red cell as well as provide supporting structure for more than 30 red cell antigens.3 Ions and gases move across the red cell membrane in an organized and harmonious fashion. Water (H2O), chloride (Cl), and bicarbonate (HCO3) diffuse freely across the red cell membrane as a result of specialized channels, like aquaphorins. Other ions like sodium (Na+), potassium (K+), and calcium (Ca2+) are more highly regulated by a careful intracellu-lar-to-extracellular balance. For sodium, the ratio is 1:12, and for potassium, 25:1,4 the ratio that represents the amount of sodium and potassium transport in and out of the cell. This ratio is the optimum ratio for red cell survival and is controlled by cationic energy pumps requiring ATP for Na+ and K+ and by calmodulin, which regulates calcium migration through the cal-cium-ATPase pumps. If the membrane becomes more permeable to Na+, rigid red cells may develop leading to spherocytes, which have a decreased life span. Red cells, which are more water permeable, may hemolyze and burst prematurely, again leading to reduced life span. Glycophorins A, B, and C are additional integral membrane proteins, containing 60% carbohydrates and most of the membrane sialic acid, which imparts a net negative charge to the red cell surface. Many red cell antigens are located on this portion of the membrane. Red cell antigens M and N are located on glycophorin A, while red cell antigens S and s are located on gly-cophorin B. Glycophorin C provides a point of attachment to the cytoskeleton or inner layer of the red cell membrane.

The Cytoskeleton

The cytoskeleton is an interlocking network of proteins that play a significant role in the deformability and elasticity of the red cell membrane. The third layer of the red cell membrane supports the lipid bilayer and also supplies the peripheral proteins. Spectrin and ankyrin are peripheral proteins that are responsible for the deformability properties of the red cell. Deformability and elasticity are crucial properties to the red cell, because the red cell with an average diameter of 6 to 8 pm must maneuver through vascular apertures like the splenic cords and capillary arterioles, which have diameters of 1 to 3 pm. Indeed, the intact and deformable red cell can stretch 117% of its surface area as it weathers the turmoil of circulation, squeezing through small spaces. Inherited abnormalities of spectrin can lead to the production of spherocytes, a more compact red cell with a reduced life span. Spectrin-deficient red cells are normal size and shaped once they exit the bone marrow. It is only when they are pushed into the systemic circulation and are subjected to the rigors of the spleen that the outer layer of the red cell membrane is shaved, leading to the more compact and damaged cell, the sphero-cyte. This particular spherocyte mechanism, which occurs in hereditary spherocytosis, best illustrates the progressive loss of membrane that occurs in hereditary spherocytosis. Once the spherocyte is reviewed by the spleen, the membrane is removed, leaving a remodeled red cell. Other mechanisms for the formation of sphero-cytes may occur, but these are discussed later.

The Prevention and Treatment of Headaches

The Prevention and Treatment of Headaches

Are Constant Headaches Making Your Life Stressful? Discover Proven Methods For Eliminating Even The Most Powerful Of Headaches, It’s Easier Than You Think… Stop Chronic Migraine Pain and Tension Headaches From Destroying Your Life… Proven steps anyone can take to overcome even the worst chronic head pain…

Get My Free Audio Book


Post a comment