Sympathetic stimulation

The phenomena of systemic cocaine poisoning are largely those of sympathetic stimulation but not as consistently as with epinephrine. The sympathetic stimulation is mainly central (midbrain) but partly peripheral. The chief manifestations of sympathetic stimulation are (1) sensitization to epinephrine (but antagonization to ephedrine) by peripheral action, (2) mydriasis and slight exophthalmos by central and peripheral action, and (3) cardiac acceleration (chiefly central). Other sympathetic symptoms are constriction of the blood vessels, erection of hair, and relaxation of the intestines. High concentrations of cocaine paralyze all smooth muscles. Procaine also produces 

The effects of cocaine on the general circulation are partly central, and partly peripheral. They vary according to the dose, and are also influenced by individual susceptibility. The systemic actions of cocaine are rather variable and complex, depending largely on the dose. 

The first systemic effects of cocaine consist in physical stimulation somewhat resembling caffeine. This differs considerably in degree and in kind with individuals and may be manifested as alertness, loquacity, elation, wakefulness, excitement (sometimes markedly sexual), or anxiety and flutter. The stimulation is greatest in excitable individuals and may interfere seriously with operations. Patients should be forewarned of the anxiety complex. 

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Explain how effects of the catecholamines differ from those of direct sympathetic stimulation... 

Tissue Sympatheticreceptor Sympathetic stimulation Parasympathetic stimulation... 

Inspection of the retina during an ophthalmoscopic examination is greatly facilitated by mydriasis, or the dilation of the pupil. Parasympathetic stimulation of the circular muscle layer in the iris causes contraction and a decrease in the diameter of the pupil. Administration of a muscarinic receptor antagonist such as atropine or scopolamine prevents this smooth muscle contraction. As a result, sympathetic stimulation of the radial muscle layer is unopposed, causing an increase in the diameter of the pupil. These agents are given in the form of eye drops that act locally and limit the possibility of systemic side effects. 

Because cardiac muscle is myogenic, nervous stimulation is not necessary to elicit the heart beat. However, the heart rate is modulated by input from the autonomic nervous system. The sympathetic and parasympathetic systems innervate the SA node. Sympathetic stimulation causes an increase in heart rate or an increased number of beats/min. Norepinephrine, which stimulates ( -adrenergic receptors, increases the rate of pacemaker depolarization by increasing the permeability to Na+ and Ca++ ions. If the heart beat is generated more rapidly, then the result is more beats per minute. 

Sympathetic stimulation increases heart rate. Norepinephrine, the neurotransmitter released from sympathetic nerves, binds to the (3-adrenergic receptors in the heart and causes the following effects ... 

The second factor that exerts control on heart rate is the release of the catecholamines, epinephrine and norepinephrine, from the adrenal medulla. Circulating catecholamines have the same effect on heart rate as direct sympathetic stimulation, which is to increase heart rate. In fact, in the intact heart, the effect of the catecholamines serves to supplement this direct effect. In a denervated heart, circulating catecholamines serve to replace the effect of direct sympathetic stimulation. In this way, patients who have had a heart transplant may still increase their heart rate during exercise. 

During exercise when sympathetic stimulation to the heart is increased, the ejection fraction may increase to more than 80% resulting in greater stroke volume and cardiac output. 

Explain how blood volume, sympathetic stimulation of the veins, skeletal muscle activity, and respiratory activity influence venous return... 

The sympathetic system innervates most tissues in the heart including the SA node, AV node, and ventricular muscle. Sympathetic stimulation causes an increase in HR as well as an increase in ventricular contractility, which... 

The sympathetic system also innervates vascular smooth muscle and regulates the radius of the blood vessels. All types of blood vessels except capillaries are innervated however, the most densely innervated vessels include arterioles and veins. An increase in sympathetic stimulation of vascular smooth muscle causes vasoconstriction and a decrease in stimulation causes vasodilation. Constriction of arterioles causes an increase in TPR and therefore MAP. Constriction of veins causes an increase in venous return (VR) which increases end-diastolic volume (EDV), SV (Frank-Starling law of the heart), CO, and MAP. 

Because baroreceptors respond to stretch or distension of the blood vessel walls, they are also referred to as stretch receptors. A change in blood pressure will elicit the baroreceptor reflex, which involves negative feedback responses that return blood pressure to normal (see Figure 15.6). For example, an increase in blood pressure causes distension of the aorta and carotid arteries, thus stimulating the baroreceptors. As a result, the number of afferent nerve impulses transmitted to the vasomotor center increases. The vasomotor center processes this information and adjusts the activity of the autonomic nervous system accordingly. Sympathetic stimulation of vascular smooth muscle and the heart is decreased and parasympathetic stimulation of the heart is increased. As a result, venous return, CO, and TPR decrease so that MAP is decreased back toward its normal value. 

Sympathetic stimulation of veins. The smaller, more compliant veins that serve generally as blood reservoirs as well as specific blood reservoirs are densely innervated by the sympathetic system. Stimulation of the vascular smooth muscle in the walls of these vessels causes vasoconstriction and a decrease in venous compliance. Vasoconstriction increases venous pressure in the veins the blood is squeezed out of the veins and, due to the presence of one-way valves, moves toward the heart so that VR increases. A decrease in sympathetic stimulation allows the veins to relax and distend. The vessels become more compliant and capable of holding large volumes of blood at low pressures. In this case, VR decreases. 

The effect of sympathetic stimulation on venous resistance is minimal. As previously stated, it is the larger, less flexible veins that provide resistance to blood flow. However, these blood vessels are sparsely innervated therefore, little change takes place in vessel radius and physiological effect on blood flow is relatively insignificant. 

Sympathetic stimulation of the veins and other blood reservoirs results in ... 

In other words, the increase in cardiac output occurs by extrinsic (sympathetic stimulation) and intrinsic (increased VR and the Frank-Starling law of the heart) mechanisms. Venous return is also markedly increased by the compression of blood vessels in the working muscles. TTie increase in CO causes an increase in MAP, and the increase in MAP contributes to an increase in muscle blood flow. 

Most arterioles of the peripheral circulation are strongly constricted by direct sympathetic stimulation. This widespread vasoconstriction serves two purposes. First, it contributes to the increase in MAP. Second, it is an important factor in the redirection of blood flow away from inactive tissues and toward the working muscles. 

However, the degree of sympathetic stimulation to the kidneys is altered under various physiological and pathophysiological conditions. For example, consider a case in which an individual is volume depleted due to hemorrhage or dehydration ... 

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). 

Sympathetic stimulation also increases the resistance of the efferent arteriole, leading to a decrease in blood pressure in the peritubular capillaries. This fall in pressure facilitates movement of sodium and water from the tubules into these capillaries. 

Sympathetic stimulation of adrenergic receptors on the granular cells of the juxtaglomerular apparatus promotes secretion of renin and, consequently, formation of angiotensin II. Angiotensin II then causes ... 

Constriction Angiotensin II Sympathetic stimulation Endothelin Adenosine Vasopressin Prostaglandin blockade Dilatation Angiotensin II blockade Prostaglandins Reduced GFR... 

Angiotensin-II AT, Human cDNA Artherosderosis, cardiac hypertrophy, congestive heart failure, hypertension, myocardial infarction, renal disease, cancer, diabetes, obesity, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Smooth muscle contraction, cell proliferation and migration, aldosterone and ADH release, central and peripheral sympathetic stimulation, extracellular matrix formation, tubular sodium retention, neuroprotection... 

Stimulation of saliva production is under sympathetic and parasympathetic control. Parasympathetic stimulation produces a serous watery secretion, whereas sympathetic stimulation produces much thicker saliva. Drug delivery systems, therefore, should not be placed over a duct or adjacent to a salivary duct, as this may dislodge the retentive system or may result in excessive wash-out of the drug or rapid dissolution/erosion of the delivery system making it difficult to achieve high local drug concentrations. If a retentive system is placed over salivary ducts, the reduced salivary flow rate may produce less or no mucus which is required for the proper attachment of a mucoadhesive delivery device. 

Cardiac failure Sympathetic stimulation is a vital component supporting circulatory function in CHF, and -blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. 

Cardiac failure Sympathetic stimulation may be essential for circulation support in diminished myocardial contractility its inhibition by -receptor blockade may precipitate more severe failure. 

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