FORMATION OF TISSUE FLUID AND EXCHANGE OF MATERIALS IN THE CAPILLARY NETWORK
In a capillary network, two opposing forces mainly determine the movement of fluid between the blood and tissue fluid:
- the hydrostatic pressure difference
- the osmotic potential difference between the blood and the tissue fluid.
In the part of the capillary network near the arterial end, blood pressure is much higher than that of the tissue fluid so that the difference in hydrostatic pressure exceeds the osmotic difference between the two fluids. As a result, some plasma is filtered out of the capillaries under pressure into the tissue space to form tissue fluid. As blood moves along the narrow capillaries, the blood pressure drops continuously so that the difference in hydrostatic pressure between the blood and tissue fluid decreases steadily or may even be reversed.
At the venous end of the capillary network, most the tissue fluid formed at the arterial end is reabsorbed back into the capillaries by osmosis This mechanism results in a continuous formation of tissue fluid from the plasma by filtration and the return of tissue fluid back to the blood by osmosis. This circulation of tissue fluid is essential for the regulation of blood pressure and blood volume.
For instance, when there is a drop in blood pressure such as due to hemorrhage, less tissue fluid would be formed at the arterial end and more tissue fluid will be absorbed back into the blood at the venous end of the capillary network. The net flow of tissue fluid into the capillary network results in a rise in blood volume and blood pressure to normal .
The opposite occurs when the blood pressure or blood volume increases. When the osmotic potential of the blood is raised, e.g. due to a low plasma protein level, the osmotic difference between the blood and tissue fluid decreases. This results in a net formation of tissue fluid from the plasma as the volume of tissue fluid formed exceeds that returned to the plasma As the tissue fluid volume (about 10 litters) is three to four times larger than the volume of plasma (About 3 liters), the tissue fluid serves as a reservoir which can supply additional fluid to the Circulatory system or draw off excess. This mechanism of tissue fluid formation and withdrawal is Important in maintaining a constant plasma volume. This process, however, plays a relatively minor role in the exchange of nutrients and metabolic Wastes between the blood and the tissue.
Although some nutrients and wastes are carried by mass Flow during this fluid movement, most nutrients and metabolic wastes are transported between blood and tissue cells by diffusion according to the concentration gradient of these substances. Thus Glucose diffuses from the blood to the tissue cells across the capillary wall along the whole length of the capillary network not just restricted to the arterial end. Similarly, waste substances produced by The body cells diffuse into the blood along the capillaries in the opposite direction this Process of diffusion is facilitated by the very thin capillary wall and the numerous branches of the Capillary network which present a very large surface area for diffusion to occur.
The low rate of Blood flow along the capillaries also allows enough time for diffusion to take place. Many local textbooks elaborate on the formation of tissue fluid but give little description on the Diffusion of substances between the blood and the tissue. Thus many students develop the mistaken Belief that the formation and absorption of tissue fluid in the capillary network is essential for the Transport of materials between blood and body cells, and fail to appreciate the importance of diffusion in the exchange of materials in the capillary network.
ADAPTIVE FEATURES OF THE CAPILLARY NETWORK
It is a well known fact that blood flows very slowly along the capillaries and this low flow rate Facilitates the exchange of materials by diffusion between the blood and tissue fluid. In accounting for The low blood flow rate in the capillaries, many students wrongly think that it is due to the narrow Diameter of the capillaries, which presents a high resistance to blood, flow.
In a closed circulation, it must be realized that the volumes of blood flowing through any cross section Of the circulatory system per unit time (V) is constant, and the flow rate of the blood at different Points of the system varies according the following relationship:V = A X RWhere A is the total cross sectional area at any point and R is the flow rate of blood at this point.
As V is constant at all points of the circulatory system; it follows that the flow rate is inversely Proportional to A. The very low rate of blood flow in a capillary network is therefore a result of the Large total cross-sectional area rather than due to the narrow diameter of the capillaries. The very Narrow diameter of the capillaries results in a high resistance to blood flow, and this leads a Significant drop in the blood pressure along the capillaries. However, this rapid drop of blood Pressure in the capillaries does not affect the blood flow rate in this region, which is inversely Proportional to the total cross-sectional.
The blood velocity is very high in the aorta, becomes progressively lower in the Arteries and arterioles, and then drops rapidly to a low level as it pass through the capillaries, Which have a total cross-sectional area 1000 times that of the aorta. The speed then increases steadily in the venues and veins as the cross-sectional area Decreases.
The significance of the very slow blood flow in the capillaries (0.07 cm per second) is that it allows adequate time for the exchange of nutrients and metabolic wastes between the blood and tissue cells by diffusion. Irrespective of the total cross-sectional area and the resistance of the Blood vessels; blood always flows along a concentration gradient, i.e. from a point of higher Pressure to that of lower pressure.
The greater the resistance to blood flows between these two Points, the greater will be the drop in blood pressure as blood moves along. In a closed system such as the circulatory system, the rate of fluid flow at any point is not determined By the pressure at that point, but by its relative total cross-sectional area. Thus blood flow rate is Lowest at the capillary network because of its large total cross-sectional area.
On the other hand, the High resistance of the narrow and numerous capillaries does not affect the blood flow rate at the Capillaries, but will result in a rapid drop in blood pressure along the capillaries as more energy is Required moving the blood along this part. To help students to integrate the above ideas, the table below provides a summary of the adaptive Features of the capillaries and their significance: Adaptive features of capillaries and their significance, Adaptive features Effect Significance
Two thousand people in the U.S. are diagnosed each year with plastic anemia. The symptoms of plastic anemia are fatigue, bruising, infections, and weakness. Although these symptoms are much like those associated with leukemia. Plastic anemia is not a form of cancer. In-patients, with plastic anemia the bone marrow stops producing, or produces too few red blood cells, white blood cells, and platelets. Without sufficient red blood cells, oxygen cannot reach organs and tissues throughout the body.
A decrease in the number of white blood cells causes the body’s ability to fight infection as well as it should. Platelets are needed to help blood clot. Although the exact cause of plastic anemia is not known, most evidence points to a combination of factors. The first factor is damaged stem cells.
These are the primitive cells in the bone marrow that produce blood cells. Another factor is damage to the bone marrow environment in which blood cells develop. Other factors include abnormalities in the proteins that regulate blood cell production and a malfunctioning immune system that interferes with the normal blood cell production.
Certain environmental factors have been associated with the development of plastic anemia. Chemotherapy drugs such as busulfan or antibiotics such as chloraphenicol can cause temporary or prolonged plastic anemia. Chemicals such as benzene and pesticides, infections such as viral hepatitis and mononucleosis, autoimmune disorders and ionizing radiation also has been linked to the development of plastic anemia. Although exposure to these agents increases the risk of developing plastic anemia, it is proven that they are not the sole cause of plastic anemia. Plastic anemia was once considered incurable.
Today, more than fifty percent of patients diagnosed with plastic anemia can be cured. For patients under the age of fifty and those over fifty that are in good health, the treatment of choice is a bone marrow transplant. However, more than halves of the patients that are diagnosed are ineligible foe a bone marrow transplants because of age or the lack of a suitable bone marrow donor.
For these patients, the preferred treatment is immunosuppressive therapy consisting of injections of antithymocyte globulin (ATG), with or without oral closporine. ATG therapy boosts the production of red blood cells, blood cells, and platelets in thirty to fifty percent of patients. In some cases, blood cell production returns to normal, while in others it returns to a level that allows the patient to have a normal lifestyle.
Approximately ten to fifteen percent of patients who initially respond to ATG therapy have the disease relapse during the first twelve months following treatment. Another round of ATG therapy may be administered in an effort to bring blood cell production back to an acceptable level. Some patients who respond to ATG therapy eventually develop another bone marrow disorder such as myelogenous syndrome or acute nonmyelogenous leukemia.
These disorders may be temporarily treatable, but are seldom curable. Overall, between thirty and forty percent of patients treated with ATG therapy become long term survivors and the majority of these long term survivors appear to be cured. Patients who have a relative with matching bone marrow have a seventy to ninety percent chance of being cured following a bone marrow transplant. Patients transplanted with marrow from a related donor whose marrow type nearly matches the patient’s have a fifty- percent chance of being cured. If marrow from a matched unrelated donor is used, the likelihood of a cure is twenty to thirty percent. Physicians determine whether a donor’s marrow type matches the patient’s by examining genetic markers on the surface of white blood cells called HLA antigens.
These are the antigens that help the body identify invading organisms, and trigger an immune system attack on any substances that do not belong in that particular person’s body, such as viruses and bacteria. If the patient and donor’s HLA antigens do not match, the patient’s body will perceive the donor’s bone marrow as foreign material to be destroyed. This condition is called graft rejection and results in a failed bone marrow transplant.
The patient’s and the donor’s marrow types must also match to minimize the risk and severity of another complication called graft versus host disease. The primary complication following a bone marrow transplant for plastic anemia is graft versus host disease. In graft versus host, the donor’s bone marrow attacks the patient’s organs and tissues, impairing their ability to function, and increasing the risk of infection.
Depending on its severity, graft versus host can be a temporary inconvenience or a life threatening condition. Graft versus host is often referred to as only one disease, but in reality it is actually two closely related diseases: acute graft versus host disease and chronic graft versus host disease. Patients may develop one, both, or neither. acute graft versus host disease usually occurs within the first three months after the bone marrow transplant. Chronic graft versus host disease usually develops after the third month following the transplant.
The earliest sign of acute graft versus host disease is often a skin rash that appears on the hands or feet. It may spread to other parts of the body, developing into a general redness similar to sunburn, with peeling or blistering skin. Cramping, nausea, and watery or bloody diarrhea are also signs of acute graft versus host disease in the stomach or intestines. Jaundice indicates that graft versus host has affected the liver. Patients with chronic graft versus host disease usually experience skin problems such as a dry, itching rash, a change in skin color, on tautness or tightening of the skin.
Occasionally, patients will experience “contractors”, which are the tightening of the tendons in the joints that makes extending or contracting arms and legs difficult. Partial hair loss or premature graying may also occur. Chronic graft versus host may also attack the glands in the body that secrete mucus, saliva and other lubricants.
Patients may experience dry or stinging eyes, a dry mouth or throat, and a burning sensation in the mouth when using toothpaste or eating acidic foods. Chronic graft versus host disease, causing heartburn, stomach pain, or weight loss may affect the digestive tract. It may also affect the liver and lungs, causing wheezing, bronchitis, or pneumonia. To reduce the incidence and severity of acute graft versus host, patients are given immunosuppressive drugs.
These drugs are routinely administered for approximately six months after the bone marrow transplant and longer if the patient develops chronic graft versus host disease. The risk of developing acute graft versus host depends on the source of the bone marrow and the choice of medications given to prevent it. Fifteen to thirty percent of patients transplanted with marrow from a related donor develop acute graft versus host. In most cases, patients develop only a mild or moderate form of the disease. Approximately seventy percent of patients transplanted from an unrelated donor develop the disease.
The risk of developing chronic host versus graft depends upon the source of the marrow and the age of the patient. About thirty percent of the patients who receive marrow from a related donor develop the disease. About seventy percent of the patients who receive marrow from an unrelated donor develop the disease. Although most patients recover from graft versus host disease, symptoms such as skin sensitivity, eye irritation, chronic diarrhea, and less frequently, lung and liver problems or contractors, may persist long term. Most patients, however, do not experience long term debilitating side effects. Some patients transplanted for plastic anemia require a preparative regimen that includes total body irradiation (TBI).
Children given TBI have experienced slowed growth and hormone development, and are more likely to be infertile than those whose preparative steps did not include TBI. Patients of all ages have a greater risk of developing a secondary cancer following TBI than other patients develop. Still, the overall chance of having a secondary cancer is very low. Norma Ramose of the University of Minnesota Hospitals states, “The treatment of severe plastic anemia with bone Marrow transplantation is truly one of modern day medicine’s major success stories”.
The treatment for plastic anemia has improved greatly over the past two decades. Prior to 1970, only ten percent of patients lived more than a year after diagnosis. Now, approximately eighty percent of the patients are alive three to five years after diagnosis. In conclusion, what I have learned is valuable to most and all of my knowledge many of the diseases that I have researched a bout over time is blood related.
