Vascular system function

Several chemical compounds can have an adverse effect on the heart and the vascular system. The effect may first appear as a transient change in the cardiac function. However, prolonged exposure increases the risk of permanent effects. Occasionally, functional effects such as cardiac arrhythmias may even lead to death. Furthermore, in many cases the effects of chemicals... 

The pathophysiologic mechanisms of portal hypertension and of cirrhosis itself are entwined with the mechanisms of ascites (Fig. 19-3). Cirrhotic changes and the subsequent decrease in synthetic function lead to a decrease in production of albumin (hypoalbuminemia). Albumin is the major intravascular protein involved in maintaining oncotic pressure in the vascular system low serum albumin levels and increased capillary permeability allow fluid to leak from the vascular space into body tissues. This can result in peripheral edema, ascites, and fluid in the pulmonary system. The obstruction of hepatic sinusoids and... 

Although most drugs are absorbed from the intestine by the blood capillary network in the villi, they can also be taken up by the lymphatic system (an integral and necessary part of the vascular system, the function of which is to collect extra tissue fluid and return it to the vascular compartment), particularly by M cells that reside in the Peyer s patch regions of the intestine. Peyer s patches have also been implicated in the regulation of the secretory immune response. Wachsmann et al. [277] reported that an antigenic material encapsulated within a liposome, when administered perorally, is taken up by these M cells and exhibited better saliva and serum IgA (primary and secondary)... 

Platelets play a role in each of the mechanisms of normal hemostasis vasoconstriction, formation of the platelet plug, and blood coagulation. However, they are also involved in pathological processes that lead to atherosclerosis and thrombosis (formation of a blood clot within the vascular system). Antiplatelet drugs interfere with platelet function and are used to prevent the development of atherosclerosis and formation of arterial thrombi. 

In addition to its osmoregulatory function, HSA serves a transport function. Various metabolites travel throughout the vascular system predominantly bound to HSA. These include fatty acids, amino acids, steroid hormones and heavy metals (e.g. copper and zinc), as well as many drugs. 

Bone metabolism has quickly become a topic of fascinating research. The bone, far from being a metabolically inactive tissue, is a tissue where different cell types and different molecules carry out numerous and varied functions. This has been due largely to the discovery of the RANKL/RANK/OPG system of cytokines. These new molecules are decisive in OCS, bone metabolism, and bone loss, but they are also important for other tissues and cells. Indeed, these proteins are critical in several systems the immune system, where they have functions that affect cell survival and the immunomodulation of T-, B-, and dendritic cells the vascular system and the endocrine system. 

In addition to its pump function, the heart is also a secretory organ. Cardiac cells produce two small peptides, the natriuretic factors, which oppose the vasoconstrictive actions of noradrenaline (norepinephrine) from the sympathetic nervous system and of the peptide angiotensin II. By causing vasodilation and natriuresis (increased excretion of sodium in the urine), atrial natriuretic peptide (ANP) secreted from the atria and B-type natriuretic peptide (BNP) secreted by both atria and probably more significantly, from the ventricles, reduce blood pressure. The stimulus to secretion of natriuretic peptides is wall stretch of the chambers of the heart, indicating volume and pressure overload of the vascular system. A third member of the natriuretic peptide family, CNP, is secreted by endothelial cells. 

The plasma level of fatty acids in a fed subject is between 0.3 and 0.5 mmol/L. As discussed above, the maximal safe level is about 2 mmol/L. This is not usually exceeded in any physiological condition since, above this concentration, that of the free (not complexed with albumin) fatty acids in the blood increases markedly. This can then lead to the formation of fatty acid micelles which can damage cell membranes the damage can cause aggregation of platelets and interfere with electrical conduction in heart muscle (Chapter 22). The cells particularly at risk are the endothelial cells of arteries and arterioles, since they are directly exposed to the micelles, possibly for long periods of time. Two important roles of endothelial cells are control of the diameter of arterioles of the vascular system and control of blood clotting (Chapter 22). Damage to endothelial cells could be sufficiently severe to interfere with these functions i.e. the arterioles could constrict, and the risk of thrombosis increases. Both of these could contribute to the development of a heart attack (Chapter 22) (Box 7.4). 

A typical clearance profile and curve-fitting of these bioconjugates in a rat with normal renal function is shown in Fig. 16. The time constant is the relevant quantifiable measure for how fast the agent clears from the vascular system. Figs. 17 and 18 compare the plasma clearance profile of different fluorescein conjugates in normal and ligated rat kidneys. The clearance profile followed the... 

It is suspected that these drugs selectively bind with the intracellular surface of sodium channels and block the entrance of sodinm ions into the cell. This leads to stoppage of the depolarization process, which is necessary for the diffusion of action potentials, elevation of the threshold of electric nerve stimulation, and thus the elimination of pain. Since the binding process of anesthetics to ion channels is reversible, the drug diffuses into the vascular system where it is metabolized, and nerve cell function is completely restored. 

The sympathetic nervous system plays an important role in the involuntary regulation of cardiac activity, vascular tonicity, functional activity of smooth muscle, and glands by releasing endogenic adrenergic substances, cateeholines, from peripheral nerve endings into the synapses of the central nervous system (CNS). 

The majority of blood substitutes currently in use function only as plasma expanders. These maintain blood pressure by providing vascular fluid volume after haemorrhage, burns, sepsis or shock. While standard electrolyte solutions, such as physiological saline, may be administered, their elfect is transitory as they subsequently dilfuse back out of the vascular system. 

Ideally, the distribution of osmotic diuretics should be largely confined to the vascular system, although this can lead to excessive expansion of the vascular compartment. Such an overexpansion could precipitate pulmonary edema or increase cardiac work or both. This is largely the result of rapid transfer of fluid from the interstitial to the vascular compartment. Practically speaking, however, few osmotic diuretics are available for therapeutic use. These agents, therefore, should be given cautiously to patients with compromised cardiac function. 

In most cases, elevated blood pressure is associated with an overall increase in resistance to flow of blood through arterioles, while cardiac output is usually normal. Meticulous investigation of autonomic nervous system function, baroreceptor reflexes, the renin-angiotensin-aldosterone system, and the kidney has failed to identify a primary abnormality as the cause of increased peripheral vascular resistance in essential hypertension. 

As larger amounts of complexes are infused into experimental animals, the rate of clearance slows and vascular lesions appear, presumably as a result of overload (B9, HI, H2). Similar phenomena may occur in man, and impaired clearance has been demonstrated in several diseases associated with manifestations of immune complex deposition including systemic lupus erythematosus (F9, H8, K9, L19, P2), primary biliary cirrhosis (G19), Sjogren s syndrome (H9), and dermatitis herpetiformis (L6). Impaired clearance may be a result of circulatory overload by immune complexes, or a primary defect in mononuclear phagocytic system function may contribute or predispose to immune complex deposition (A15, A16, HI). However, impaired clearance, as currently measured, is neither a prerequisite nor a consistent consequence of immune complex disease. 

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