Platelets and Plasma

Platelets, or thrombocytes, are not complete cells. They arise from very large cells in red bone marrow, called megakaryocytes. These cells release cytoplasmic fragments of themselves, and as the fragments detach and enter the circulation, the smaller ones become platelets. As they pass through the blood vessels of the lungs, the larger fragments break down to produce more platelets.

Earth platelets is a round disk that lacks a nucleus and is less than half the size of a red blood cell. It is capable of amoeboid movement and may live for about ten days. In normal human blood, the platelet count will vary from 130,000 to 360,000 platelets per mm3.

Platelets help close the breaks in damaged blood vessels and function to initiate the formation of blood clots, as is explained in a subsequent section of this chapter.

Plasma is the clear, straw-colored, liquid portion of the blood in which the cells and platelets are suspended. It is approximately 92 percent water and contains a complex mixture of organic and inorganic substances that function in a variety of ways. These functions include transporting nutrients, gases, and vitamins; regulating fluid and electrolytes balances; and maintaining a favorable pH.

The most abundant of the dissolved substances (solutes) in plasma are the plasma proteins. These proteins remain in the blood and interstitial fluids and ordinarily are not used as energy sources. The three main groups are albumins, globulin's, and fibrinogen. The members of each group differ in their chemical structures and in their physiological functions.

Albumin's account for about 60 percent of the plasma proteins and their molecules are the smallest of these proteins. Albumin's are synthesized in the liver, and because they are so plentiful, albumin's together with other solutes, help maintain the osmotic pressure of the blood.

As explained in chapter 3, whenever the concentration of solutes changes on either side of a cell membrane, water is likely to move through the membrane toward the region where the dissolved molecule are in higher concentration. For this reason, it is important that the concentration of solutes in the plasma remain relatively stable. Otherwise, water tends to leave the blood and enter the tissues or to leave the tissues and enter the blood by osmosis. Because albumin's (and other plasma proteins) add to the osmotic pressure of the plasma, they aid in regulating the water balance between the blood and tissues. At the same time, they help control the blood volume, which, in turn, is directly related to the blood pressure.

Globulin's, which make up about 36 percent of the plasma proteins, can be separated further into fractions called alpha globulin's, beta globulin's, and gamma globulin's. Alpha and beta globulin's are synthesized in the liver, and the have a variety of functions including the transport of lipids and fat-soluble vitamins. Gamma globules are produced in the lymphatic tissues, and they include the proteins that function as antibodies of immunity.

Fibrinogen, which constitutes about 4 percent of the plasma proteins, play a primary role in the blood clotting mechanism. It is synthesized in the liver and has the largest molecules of the plasma proteins. Its function is described in a subsequent section of this chapter.

The plasma nutrients include amino acids, simple sugars, and various lipids that have been absorbed from the digestive tract and are being transported to organs and tissues by the blood. Glucose, for example, is transported by the plasma from the small intestine to the liver, where it may be stored as glycogen or changed into fat. If the blood glucose concentration drops below the normal range, glycogen may be converted back into glucose.

Recently absorbed amino acids are also carried to the liver, where they may be used in the manufacture of proteins such as those found in the plasma, or deaminated and used as an energy source.

The lipids of plasma include fats (triglycerides), phospholipids, and cholesterol. These lipids, which tend to be insoluble in water, are combined with proteins in complexes called lipoproteins, and they help transport lipids in the blood. Lipoprotein molecules are relatively large and consist of a core of triglyceride surrounded by a surface layer composed of phopholipid, cholesterol, and protein. Within the protein portion of this layer are specialized molecules called apoproteins that can combine with receptors on the membranes of specific target cells. Lipoprotein molecules also vary in the proportions of the various lipids they contain.

Because fats are less dense than proteins, as the proportion of triglycerides in a lipoprotein increases, the density of the particle decreases. Conversely, as the proportion of triglycerides decreases, the density increases.

On the basis of their densities, which reflect their composition, lipoproteins can be classified as chylomicrons, which consist mainly of triglycerides absorbed from the small intestine.

After chylomicrons have delivered their triglycerides to cells, the remnants of these molecules are transferred to high-density lipoproteins. These HDL molecules, which are formed in the liver and small intestine, transport chylomicron remnants to the liver, where they enter cells rapidly by endocytosis. The liver disposes of the cholesterol it obtains in this manner by secreting it into bile or by using it to synthesize bile salts.

Much of the cholesterol and bile salts in bile are later reabsorbed by the small intestine and transported back to the liver, and the secretion-reabsorption cycle is repeated. During each cycle, some of the cholesterol and bile salts escape reabsorption, reach the large intestine, and are eliminated with the feces.

The most important blood gases are oxygen and carbon dioxide. Although the plasma also contains a considerable amount of dissolved nitrogen, this gas ordinarily has no physiological function.

Molecules that contain nitrogen atoms but are not proteins comprise a group called non protein nitrogenous substances. Within the plasma, this group includes amino acids, urea, and uric acid. The amino acids are present as result of protein digestion and amino acid absorption. The urea and uric acid are the products of protein and nucleic acid catabolism, respectively, and are excreted in the urine.

The plasma contains a variety of electrolytes, which have been absorbed from the intestine or have been released as by-products of cellular metabolism. They include sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate, and sulfate ions. Of these, sodium and chloride ions are the most abundant.

Such ions are important in maintaining the osmotic pressure and the pH of the plasma, and like other plasma constituents, they are regulated so that their blood concentrations remain relatively stable. These electrolytes are discussed in chapter 18 in connection with water and electrolyte balance.

The term hemostasis refers to the stoppage of bleeding, which is vitally important when blood vessels are ruptured. Following an injury to blood vessels, several actions may occur that help prevent excessive blood loss. These include blood vessel spasm, platelet plug formation, and blood coagulation.

When a blood vessel is cut or broken, the smooth muscles in its wall are stimulated to contract, and blood loss is decreased almost immediately. In fact, the ends of a severed vessel may be closed completely by such a vasospasm.

Although this response may last only a few minutes, by then the platelet plug and the blood coagulation mechanism are normally operating. Also, as a platelet plug forms, the platelets release a substance called serotonin, which causes the smooth muscles in the blood vessel wall to contract. This vasoconstricting action helps to maintain a prolonged vascular spasm.

Platelets tend to stick to any rough surface and to the collagen in connective tissue. consequently, when a blood vessel is broken, the platelets adhere to the collagen that underlies the lining of the blood vessel. At the same time, they tend to stick to each other, forming a platelet plug in the vascular break. Such a plug may be able to control blood loss if the break is relatively small.

Coagulation, which is the most effective of the hemostatic mechanisms, causes the formation of a blood clot.

The mechanism by which the blood coagulates is very complex and involves many substances called clotting factors. Some of these factors promote coagulation, and other inhibit it. Whether or not the blood coagulates depends on the balance that exists between these two groups of factors. Normally the anticoagulants prevail, and the blood does not clot. As a result of injury (trauma), however, substances that favor coagulation may increase in concentration, and the blood may coagulate.

The basic event in blood clot formation is the conversion of the soluble plasma protein fibrinogen into the relatively insoluble threads of the protein fibrin.

When tissues are damaged, the clotting mechanism initiates a series of reactions resulting in the production of a substance called prothrombin activator. This series of changes depends upon the presence of calcium ions as well as certain proteins and phospholipids for its completion.

Prothrombin is an alpha globulin that is continually produced by the liver and, thus, is normally present in the plasma. In the presence of calcium ions, prothrombin is converted into thrombin by the action of prothrombin activator. Thrombin, in turn, acts as an enzyme and causes a reaction in the molecules of fibrinogen. As a result, the fibrinogen molecules join, end to end, forming long threads of fibrin. The production of fibrin threads is also enhanced by the presence of calcium ions and certain proteins.

Once the threads of fibrin have formed, they tend to stick to the exposed surfaces of the damaged blood vessels and create a meshwork in which various blood cells and platelets become entangled. The resulting mass is a blood clot, which may effectively block a vascular break and prevent further loss of blood.

The amount of prothrombin activator that appears in the blood is directly proportional to the degree of tissue damage. Once a blood clot begins to form, it promotes still more clotting. This happens because thrombin also acts directly on blood-clotting facts other than fibrinogen, and it can cause prothrombin to form still more thrombin. This is an example of a positive feedback system, in which the original action stimulates more of the same type of action. Such a positive feedback mechanism produces very unstable conditions and can operate for only a short time in a living organism.

Normally, the formation of a massive clot through-out the blood system is prevented by the blood's movement, which rapidly carries excessive thrombin away and, thus, keeps its concentration too low to enhance further clotting. As a result, blood clot formation is usually limited to the blood that is standing still (or moving relatively slowly), and clotting ceases where a clot comes in contact with circulating blood.

Blood clots that form in ruptured vessels are soon invaded by fibroblasts. These cells produce fibrous connective tissue throughout the clots, which helps strengthen and seal vascular breaks. Many clots, including those that form in tissues as a result of blood leakage (hematomas), disappear in time. This dissolution involves the activation of plasma protein that can digest fibrin threads and other proteins associated with clots. Clots that fill large blood vessels, however, are seldom removed by natural processes.

If a blood clot forms in a vessel abnormally, it is termed a thrombus. If the clot becomes dislodged or if a fragment of it breaks loose and is carried away by the blood flow, it is called an embolus. Generally, emboli continue to move until they reach narrow places in vessels where they become lodged and may interfere with the blood flow.

Such abnormal clot formations are often associated with conditions that cause changes in the endothelial linings of vessels. In the disease called atherosclerosis, for example, arterial linings are changed by accumulations of fatty deposits. These changes may initiate the clotting mechanism.