Plasma volume regulation

A low thyroid function can influence many of the neuro-humoral systems involved in vascular tone and plasma volume regulation. It has long been known that chronic hypothyroid patients show an increase in peripheral arterial resistance. This is principally due to the lack of direct T3-dependent vasorelaxation and to an increase in arterial wall thickness (Cappola and Ladenson, 2003 Rawat and Satyal, 2004), but enhanced sympathetic activity may also contribute significantly to peripheral vasoconstriction, probably as a powerful compensatory mechanism for the decreased cardiac contractility and intravascular volume which follows TH deprivation. The enhanced sympathetic efflux may eventually overcome a downregulation of post-synaptic vasoconstrictor a-adrenoreceptors, which is described in hypothyroid states, at variance with what is observed in normal physiology, where a positive relationship does exist between TH and the number and activities of noradrenergic receptors (Gomberg-Maitland and Frishman, 1998). 

Plasma protein fractions include human plasma protein fraction 5% and normal serum albumin 5% (Albuminar-5, Buminate 5%) and 25% (Albuminar-25, Buminate 25%). Plasma protein fraction 5% is an IV solution containing 5% human plasma proteins. Serum albumin is obtained from donated whole blood and is a protein found in plasma The albumin fraction of human blood acts to maintain plasma colloid osmotic pressure and as a carrier of intermediate metabolites in the transport and exchange of tissue products. It is critical in regulating the volume of circulating blood. When blood is lost from shock, such as in hemorrhage, there is a reduced plasma volume. When blood volume is reduced, albumin quickly restores the volume in most situations. 

Bulk flow plays only a minor role in the exchange of specific solutes between blood and tissue cells. A far more important function of bulk flow is to regulate distribution of extracellular fluid between the vascular compartment (plasma) and the interstitial space. Maintenance of an appropriate circulating volume of blood is an important factor in the maintenance of blood pressure. For example, dehydration and hemorrhage will cause a decrease in blood pressure leading to a decrease in capillary hydrostatic pressure. As a result, net filtration decreases and net reabsorption increases, causing movement, or bulk flow, of extracellular fluid from interstitial space into the vascular compartment. This fluid shift expands the plasma volume and compensates for the fall in blood pressure. 

Explain how the control of sodium excretion regulates plasma volume... 

Although the kidneys are not considered endocrine glands per se, they are involved in hormone production. Erythropoietin is a peptide hormone that stimulates red blood cell production in bone marrow. Its primary source is the kidneys. Erythropoietin is secreted in response to renal hypoxia. Chronic renal disease may impair the secretion of erythropoietin, leading to development of anemia. The kidneys also produce enzymes. The enzyme renin is part of the renin-angiotensin-aldosterone system. As will be discussed, these substances play an important role in the regulation of plasma volume and therefore blood pressure. Other renal enzymes are needed for the conversion of vitamin D into its active form, 1,25-d i hyd ro xyv itamin D3, which is involved with calcium balance. 

The maintenance of plasma volume and plasma osmolarity occurs through regulation of the renal excretion of sodium, chloride, and water. Each of these substances is freely filtered from the glomerulus and reabsorbed from the tubule none is secreted. Because salt and water intake in the diet may vary widely, the renal excretion of these substances is also highly variable. In other words, the kidneys must be able to produce a wide range of urine concentrations and urine volumes. The most dilute urine produced by humans is 65 to 70 mOsm/1 and the most concentrated the urine can be is 1200 mOsm/1 (recall that the plasma osmolarity is 290 mOsm/1). The volume of urine produced per day depends largely upon fluid intake. As fluid intake increases, urine output increases to excrete the excess water. Conversely, as fluid intake decreases or as an individual becomes dehydrated, urine output decreases in order to conserve water. 

Recall that the reabsorption of Na+ ions is accompanied by reabsorption of Cl- ions, which diffuse down their electrical gradient, and by reabsorption of water, which diffuses down its osmotic gradient. The net result is an expansion of plasma volume and consequently an increase in blood pressure. Therefore, the regulation of sodium reabsorption is important in the long-term regulation of blood pressure. As such, aldosterone and ANP, as well as the factors involved in their release, are discussed further in subsequent sections. 

Production of urine of varying concentrations. In order to regulate plasma volume and osmolarity effectively, the kidneys must be able to alter the volume and concentration of the urine that is eliminated. Accordingly, the concentration of urine may be varied over a very wide range depending upon the body s level of hydration. The most dilute urine produced by the kidneys is 65 to 70 mOsm/1 (when the body is overhydrated) and the most concentrated urine is 1200 mOsm/1 (when the body is dehydrated). (Recall that plasma osmolarity is 290 to 300 mOsm/1.)... 

Renal blood flow has a direct effect on GFR, which in turn has a direct effect on urine output. As RBF increases, GFR and urine output increase. Conversely, as RBF decreases, GFR and urine output decrease. Furthermore, any change in urine output affects plasma volume and blood pressure. Therefore, the regulation of RBF and GFR are important considerations. According to Ohm s law (Q = AP/R), RBF is determined by mean arterial pressure (MAP) and the resistance of the afferent arteriole (Raffart) ... 

Loss of plasma volume leads to a decrease in MAP. Baroreceptors located in the aortic and carotid sinuses detect this fall in MAP and elicit reflex responses that include an increase in the overall activity of the sympathetic nervous system. Sympathetic stimulation of the heart and blood vessels leads to an increase in cardiac output (CO) and increased total peripheral resistance (TPR). These adjustments, which increase MAP, are responsible for the short-term regulation of blood pressure. Although increases in CO and TPR are effective in temporary maintenance of MAP and blood flow to the vital organs, these activities cannot persist indefinitely. Ultimately, plasma volume must be returned to normal (see Table 19.1). 

Sodium is the major extracellular cation. Because of its osmotic effects, changes in sodium content in the body have an important influence on extracellular fluid volume, including plasma volume. For example, excess sodium leads to the retention of water and an increase in plasma volume. Increased plasma volume then causes an increase in blood pressure. Conversely, sodium deficit leads to water loss and decreased plasma volume. A decrease in plasma volume then causes a decrease in blood pressure. Therefore, homeostatic mechanisms involved in the regulation of plasma volume and blood pressure involve regulation of sodium content, or sodium balance, in the body. 

Sodium is freely filtered at the glomerulus. Therefore, any factor that affects GFR will also affect sodium filtration. As discussed previously, GFR is directly related to RBF. In turn, RBF is determined by blood pressure and the resistance of the afferent arteriole (RBF = AP/R). For example, an increase in blood pressure or a decrease in resistance of the afferent arteriole will increase RBF, GFR, and, consequently, filtration of sodium. The amount of sodium reabsorbed from the tubules is physiologically regulated, primarily by aldosterone and, to a lesser extent, by ANP. Aldosterone promotes reabsorption and ANP inhibits it. The alterations in sodium filtration and sodium reabsorption in response to decreased plasma volume are illustrated in Figure 19.6. 

A decrease in plasma volume leads to decreased MAP, which is detected by baroreceptors in the carotid sinuses and the arch of the aorta. By way of the vasomotor center, the baroreceptor reflex results in an overall increase in sympathetic nervous activity. This includes stimulation of the heart and vascular smooth muscle, which causes an increase in cardiac output and total peripheral resistance. These changes are responsible for the short-term regulation of blood pressure, which temporarily increases MAP toward normal. 

Kalra PR et al The regulation and measurement of plasma volume in heart failure. 3 Am Coll Cardiol 2002 39 1901. [PMID ... 

Vander. A. J. Control of sodium and water excretion Regulation of plasma volume and osiiiolariiy. In Vander. A. J. (ed.). Renal Physiology. Sih ed. New York. McGraw-Hill. 1995. pp. 116-144. 37. 

Besides the osmoreceptor mechanism of vasopressin release, the physiological regulation of vasopressin secretion also involves a pressure-volume mechanism that is distinct from the osmotic sensor. AVP release is regulated by baro-receptors that respond to alterations in blood volume. For example, a reduction in plasma volume or arterial pressure,... 

However, the mechanism by which minute changes in extracellular calcium could have major effects on blood pressure regulation and, consequently, on the development of primary hypertension, has not yet been fully elucidated. There is preliminary evidence that activation of the renal CaR leads to enhanced prostaglandin E2 (PGE2) synthesis, with natriuresis as a consequence. The concomitant reduction in plasma volume would then account for the blood pressure-lowering effect of elevated extracellular calcium (Wang et al. 2001). 

Plasma Collection. Human plasma is collected from donors either as a plasma donation, from which the red cells and other cellular components have been removed and returned to the donor by a process known as plasmapheresis, or in the form of a whole blood donation. These are referred to as source plasma and recovered plasma, respectively (Fig. 1). In both instances the donation is collected into a solution of anticoagulant (146) to prevent the donation from clotting and to maintain the stabiUty of the various constituents. Regulations in place to safeguard the donor specify both the frequency of donation and the volume that can be taken on each occasion (147). 

Procedures for the collection of whole blood are similar throughout the world. An interval from at least 8 weeks (United States) to 12 weeks (United Kingdom) is required between a donation of 450 mL blood, which yields about 250 mL plasma. In some countries a smaller volume of blood is collected, eg, 350—400 mL in Italy, Greece, and Turkey and as Httie as 250 mL in some Asian countries (147). Regulations concerning plasmapheresis donations vary more widely across the world eg, up to 300 mL of plasma can be taken in Europe in contrast to 1000 mL in the United States, both on a weekly basis. Consequentiy, both the mode of donation and the country in which it is given can have a profound effect on plasma collection (Table 6). 

One of the primary ways in which cold causes injury to cells is by the loss of the capability to regulate cellular volume. This occurs because of the decrease in the available energy (ATP) caused by hypothermia and ischemia which is needed by the membrane-bound ion pumps, the increased rate of leakage of ions through the plasma membrane, and the decreased activity of the membrane-bound ion pumps, especially the Na-pump. 

---