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Explain how the sympathetic nervous system acts to directly regulate stroke volume. Include a detailed description of the mec
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EFFECT OF SYMPATHETIC SYSTEM ON THE HEART
The Sympathetic system increases the constractility of the heart musles there by increasing the stroke volume. It acts through the Beta adrenergic receptors.
The sympathetic system releases the Noradrenalin from its post ganglionic cells. The adrenergic receptors in the cardiovascular system are β1, β2 , α1 and α2 . Their actions and effects are as given in the table 1.
Receptor    Target    Action
β1   SA node
AV node
atrial
ventricular cardiomyocytes   Increased heart rate
Increased contractility
Β2    vascular smooth muscle
skeletal muscle
coronary circulation
cardiac muscle (Low expression)   Vasodilatation
Increased heart rate
Increased contractility
α1   vascular smooth muscle
cardiac muscle (Low expression)
   Vasoconstriction
Increased heart rate
Increased contractility
α2   vascular smooth muscle
   Vasoconstriction
The β1 receptors are G protein coupled receptors (GPCR) , when nor adrenalin bind the the GPCR , the G protein dissociates and bind to and activate adenylyl cyclase (AC). AC then converts ATP into cyclic adenosine monophosphate (cAMP). cAMP activates protein kinase A (PKA), which in turn, phosphorylates multiple target proteins, such as L-type Ca channels (LTCC), the SR Ca handling protein phospholamban, and contractile machinery such as troponin C, I and T. All these effects increase the Heart rate.
Sympathetic stimulation leads to the elevation of cAMP levels and the activation of PKA, which phosphorylates the α1 subunits of the L type canclium channel (LTCC). This increases inward Ca2+ current, and thus enhances the force of cardiac contraction. Morover , activation of β1-adrenoceptors also increases the Ca2+ sensitivity for contraction. Taken together, the net result of sympathetic stimulation is to elevate cardiac function.
Overall, sympathetic system increases the cardiac contraction and increases the heart rate. Increase in contractility increases the stroke volume and they are directly related. Cardiac output is the product of strokes volume and Heart rate. As both these factors are increased by the sympathetic system , the cardiac output also increases.

VENOUS RETURN
Venous return is the amount of blood returning back to the heart . Since the cardiac system is considered a closed system , the venous return should be equal to the cardiac output over a particular time period. The factors which determine the venous return are mainly the musculo skeletal contraction of lower limbs, venous capacitance, intrathoracic pressure , venacaval compression , pumping action of heart and gravity.
When a person walks or runs , the strong muscles of the lower limb contracts and pumps the blood from the limbs back to the heart increasing the venous return. During inspiration, the negative intrathoracic pressure, and positive abdominal makes a pressure gradient between the infra and supradiaphragmatic parts of inferior venacava channeling the blood towards the right atrium and there by increasing venous return. when a person stands up the right atrial pressure decrease and the venous pressure in the dependent limbs to increase. However, venous return decreases. This is because is when a person stands, cardiac output and arterial pressure decrease because right atrial pressure falls). The flow through the entire systemic circulation falls because arterial pressure falls more than right atrial pressure; therefore the pressure gradient driving flow throughout the entire circulatory system is decreased. During the cardiac cycle right atrial pressure changes alter central venous pressure (CVP), because there is no valve between the heart's atria and the large veins. CVP reflects right atrial pressure. Therefore, right atrial pressure also alters venous return.

BODY WATER PHYSIOLOGY
The total body water is divided into intracellular compartment and extracellular compartment. Intracellular compartment forms 2/3rd of the total body water and extra cellular compartment forms the rest. The extra cellular compartment is composed of plasma , interstitial fluid and transcellular fluid . the detailed distribution and the amount in an average 72 kg human in given in table .
Intracellular fluid
2/3 of body water   about 25 litres
Extracellular fluid
1/3 of body water   15 litres


Plasma
1/5 of extracellular fluid   3 litres
Interstitial fluid
4/5 of extracellular fluid   12 litres

The major routes and water entering the body and driniking and eating.
The major routes of water loss are urine , faeces , vomiting , sweating ,breathing and bleeding. The major regulation of water in the body is through the renal system.


ANTI DIURETIC HORMONE(Vasopressin)

Vasopressin is released from the posterior pituitary in response to hypertonicity and is the major hormone involved in reabsorbtion of solute-free water. AVP released in high concentrations may also raise blood pressure by inducing moderate vasoconstriction.
The three main effects of Vasopressin are as follows :
1.   Increasing the permeability of proximal and cortical collecting tubules , outer and inner medullary collecting duct (OMCD & IMCD) in the kidney to water and thus allowing water reabsorption
This occurs through increased transcription and insertion of water channels (Aquaporin-2) into the apical membrane of collecting tubule and collecting duct epithelial cells. Aquaporins allow water to move down their osmotic gradient and out of the nephron, increasing the amount of water re-absorbed from the filtrate (forming urine) back into the bloodstream. Vasopressin also increases the concentration of calcium in the collecting duct cells, by episodic release from intracellular stores. Vasopressin, acting through cAMP, also increases transcription of the aquaporin-2 gene, thus increasing the total number of aquaporin-2 molecules in collecting duct cells.
2.   Acute increase of sodium absorption across the ascending loop of Henle. This adds to the countercurrent multiplication which aids in proper water reabsorption later in the distal tubule and collecting duct.


Normal human osmolality in plasma is about 275-299 milli-osmoles per kilogram .

Plasma osmolality increases during dehydration.

The two other systems which respond to increased plasma osmolality are the renin-angiotensin-aldosterone system and the Atrial natriuretic Peptide system.

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