Review of Medical Physiology - William F. Ganong 2002

Blood Circulation
Dynamics of Blood and Lymph Circulation
Lymph Circulation and Interstitial Fluid Volume

Lymph Circulation

Fluid filtration normally exceeds its reabsorption across the Capillary Wall; however, the excess fluid enters the Lymphatic vessels and is drained by them into the Blood. This prevents an increase in interstitial fluid pressure and ensures the turnover of tissue fluid. Under normal conditions, the 24-hour lymph flow volume is 2–4 L. The composition of lymph is described in Chapter 27. Lymphatic vessels can be divided into two types: lymphatic capillaries and collecting lymphatic vessels (Fig. 30-23). Lymphatic capillaries lack Valves and smooth Muscle in their walls; these capillaries are found in areas such as the Small Intestine and Skeletal Muscle. Tissue fluid enters the capillaries through loose junctions between the endothelial Cells that form their walls. Fluid moves within the capillaries driven by the muscular contractions of the organ and the contractions of adjacent arterioles and venules. Capillaries empty into collecting lymphatic vessels, which contain valves and smooth muscle in their walls and contract peristaltically, propelling lymph along the vessels. Lymph flow in these vessels is enhanced by skeletal muscle contractions, negative intrathoracic pressure during inspiration, and the "suction" effect resulting from the high-velocity BLOOD FLOW IN the Veins where the lymphatic vessels terminate. Nevertheless, contraction remains the primary factor driving lymph flow.

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Fig. 30-23. Lymphatic capillaries draining into mesenteric collecting lymphatic vessels. Note the close relationship with arteriole arcades, marked by the black line (reproduced with permission from Schmid-Schönbein GW, Zweifach BW: Fluid pump mechanisms in initial lymphatics. News Physiol Sci 1994;9:67).

Compounds that enhance lymph flow are called lymphagogues. They include numerous mediators that increase capillary wall permeability. Substances that induce smooth Muscle contraction also increase lymph flow from the small intestine.

Other Functions of The Lymphatic system

A significant amount of protein enters the interstitial fluid in The Liver and small intestine, with lesser amounts leaking from the blood in other Tissues. Macromolecules enter the lymphatic vessels primarily through the gaps between endothelial cells, and Proteins reach the bloodstream via the lymphatic vessels. The amount of protein transferred via this pathway in a single day equals 25–50% of the total circulating plasma protein pool. The transport of absorbed long-chain Fatty acids and Cholesterol from the small intestine via the lymphatic vessels is described in Chapter 25.

Interstitial Fluid Volume

The amount of fluid in the interstitial space depends on capillary pressure, interstitial fluid pressure, oncotic pressure, the capillary filtration coefficient, the number of active capillaries, lymph flow, and total ECF volume. The ratio of pre-capillary to post-capillary venular resistance is also of critical importance.

Pre-capillary constriction decreases filtration pressure, whereas post-capillary constriction increases it. Changes in any of these variables lead to alterations in interstitial fluid volume. Factors that promote an increase in this volume are listed in Table 30-5. Edema is the abnormal accumulation of interstitial fluid in excessive amounts.

In active tissues, capillary pressure rises, often to the point where it exceeds oncotic pressure along the length of the capillary. In addition, osmotically active metabolites sometimes temporarily accumulate in the interstitial fluid because they cannot be washed away as rapidly as they are produced. Their accumulation enhances the osmotic effect, leading to a reduction in the osmotic gradient opposing oncotic pressure. Consequently, the volume of fluid filtering out of the capillaries increases significantly, while the volume entering the blood decreases. Although lymph flow increases to compensate for fluid accumulation, in exercising muscle, for example, tissue volume still increases by about 25%.

Interstitial fluid accumulates predominantly in dependent PARTS OF THE body due to gravity. In the upright position, capillaries in the lower limbs are shielded from high arterial pressure by the arterioles, but high venous pressure is transmitted to them through the venules. Skeletal muscle contraction keeps venous pressure low by pumping blood toward The Heart (see below) during locomotion. However, standing for prolonged periods causes fluid to accumulate and edema to develop. Ankle edema is also common during long journeys when travelers sit for hours with their feet in a fixed position. Venous obstruction may contribute to edema in such situations. Regardless of its origin, sodium retention in the body is always accompanied by Water retention. Since sodium and fluid are distributed within the extracellular fluid, the interstitial fluid volume expands, Setting the Stage for edema formation. Sodium and water retention are key factors in The Development of edema in Heart Failure, nephrosis, and cirrhosis. However, other mechanisms also affect fluid movement across the capillary wall in these pathological states.

Table 30-5. Causes of increased interstitial fluid volume and edema

In congestive heart failure, for instance, venous pressure typically rises, leading to elevated capillary pressure. In liver cirrhosis, oncotic pressure decreases due to impaired hepatic Protein Synthesis; in nephrosis, oncotic pressure drops because large amounts of protein are lost in the urine.

Another cause of edema is inadequate lymphatic drainage. Edema caused by lymphatic obstruction is termed lymphedema. In this condition, the edema fluid contains a high concentration of proteins. Prolonged lymphedema leads to chronic inflammation and Connective Tissue fibrosis. One common cause of lymphedema is radical mastectomy. Performed for breast Cancer, this surgery involves the removal of unilateral axillary Lymph Nodes, thereby impairing lymphatic drainage. Edema of the arm on the side of the resected lymph nodes occurs in 10–30% of patients. In filariasis, parasitic helminths migrate into the lymphatic vessels and cause obstruction. Fluid accumulation and tissue reactions result in marked edema, typically of the legs or Scrotum (elephantiasis). The severity of these changes is vividly illustrated by a patient with elephantiasis whose scrotal edema was so massive that he had to transport it in a wheelbarrow while walking.

An interesting and effective Treatment for lymphedema is the administration of benzopyrones. These drugs enhance proteolysis by tissue macrophages. Reducing the protein content in the edema fluid helps alleviate the inflammatory response and promotes fluid reabsorption.