Physiology and pharmacology

Homeostasis means, the same – standing still, homeostasis is attempting to maintain a dynamic equilibrium, however there are multiple internal and external factors that may affect homeostasis of the human body (Cannon, 1932). Physiology allows an understanding of how the body reacts to such a change in variables. Exercise may increase body temperature and the body will react in a multitude of ways to cool itself and return the body to homeostasis. (Gray & Cooke, 2008). Enzymes are proteins that help speed up chemical reactions in cells.

Enzymes require optimum temperatures of 37oC and pH level (dependent on location) in order to function, an increased temperature will initially increase the rate of chemical reactions until such time when the enzymes become denatured, loss of solubility and communal aggregation takes place, similarly with temperatures that drop below the optimum. The active site becomes unrecognisable by its substrate in conditions beyond optimum pH and temperature thus reducing chemical reactions and life processes (Sanchez-Ruiz, 2010).

Homeostasis aims to allow the body to continue its activities of daily living regardless of the external environment or ingested products via maintenance of the internal environment. The internal environment is made up of twelve litres interstitial fluid and three litres plasma, the interstitial fluid provides cells with energy in the form of oxygen, glucose and other nutrients, cycling the waste into the blood to be filtered 1 14023982 out of the body. This highlights the need for homeostasis to maintain blood pressure at an optimum level to facilitate the profusion of blood through the tissues ensuring processes continue within the intracellular fluid (Ankney et al, 2012).

Equilibrium may be found via diffusion, being the movement of particles from an area of high concentration to that of an area with low concentration gradient, homeostasis allows diffusion to continue until such a time the factors have returned to their set limits. Osmosis is a special type of diffusion that allows water molecules to pass through a partially permeable membrane, once equilibrium is achieved in this instance, volume may be different but concentrations would be the same, the movement of molecules across the membrane at this point would be the same (Alharbi et al, 2014).

Negative feedback instigates such processes into action, either inhibiting processes or initiating others in order to return to homeostasis. Stimuli produce a change in a factor, such as an increased temperature due to exercise, the change is detected by receptors and the information is sent along afferent pathway to the control centre. Information is then sent to the effector via the efferent pathway in order to return the variable to homeostasis. Without this negative feedback loop, the temperature in this instance would rise like that in a positive feedback mechanism.

Homeostasis reverses changes, hence the term negative feedback (Keesey & Powley, 2008). 2 14023982 (2) The endocrine system assists with functions of the body, through growth, reproduction, metabolism, emotions and balancing of water and electrolytes, also dealing with adaptations to environmental changes as well as stressors. The endocrine glands of which there are many, secrete a number of hormones in order to achieve their goal and maintain homeostasis (Ankney et al, 2012). The endocrine system responds slower however the effect is longer lasting excluding the instance of a ‘fight or flight’ situation.

The stimuli is noted by the receptors, prompting hormone release, which may bring about a necessary change of the parameters of homeostasis to overcome the obstacle, in order to return to a natural homeostasis. These hormones are sent via the circulatory system and connects to the target cell via a receptor and subsequently triggers the cell to respond (Neal, 2001). With regards to a particular variable such as blood glucose, it may in first instance be regulated via the foods ingested, dependant on volume and quality that either lowers or raises the blood glucose levels.

There are a number of hormones that are released due to a homeostatic imbalance, some lower the blood glucose and other raise. Insulin is one such hormone that lowers blood glucose levels via negative feedback. Once the carbohydrates are broken down into glucose and into the bloodstream to be taken to the muscles for energy, however insulin is needed via the pancreas ? cells in order to regulate the glucose in the blood stream (Huang & Joseph, 2012). The insulin binds to the receptors on either muscle or fat cells, which in turn promotes a signal transduction cascade via a chain of phosphorylation.

Subsequent glucose transporter proteins (GLUT) are signalled and migrate towards 3 14023982 the cell surface and fuse with the cell membrane, more GLUTS arrive and allow glucose to cross the membranes into the cells at a higher rate and thus reducing the blood glucose volume (Theilman & Wendell, 2012). The glucose in combination with O2 may now be metabolised into Adenosine Triphosphate (ATP) to be used as energy. In a sedentary state the glucose will be converted by insulin into a polysaccharide called glycogen; stored in the liver and muscles.

Without the effect of insulin, hyperglycaemia will develop, the cells will receive limited energy and consequently become tired, leaving the sufferer fatigued. The body recognises the need to excrete and will do via the urinary system increasing the volume and frequency of urination (van der Berghe, 2004).

The body will achieve homeostasis of blood glucose regardless of the hormone insulin however the productivity of said person would be depleted. In reverse, with low blood glucose levels, it is called hypoglycaemia. Pancreatic ? cells secrete glucagon, stimulating the breakdown of stored glycogen into glucose in a process called glycogenolysis to achieve homeostasis of blood glucose.

However in such instance of glycogen store depletion glucagon stimulates the liver into producing additional glucose through a process called gluconeogenesis, fats from adipose tissue and protein from the muscles are synthesised into glucose (Luca & Olefsky, 2008). 4 14023982 (3) The nervous system (NS) consists of billions of cells and neurons, sending electrical impulses to ensure messages are received quickly. A neurone consists of dendrites, cell body, axon, myelin sheath and nodes of Ranvier (latter two not always present).

The myelin sheaths separate the nerve cell axons found in the peripheral NS (PNS) and central NS (CNS) allowing faster conduction and action potentials (AP), AP being the movement of ions across the neuron (Ross & Horton-Szar, 2012). The CNS is found in the brain and spinal cord, whereas the PNS stretches peripherally.

The stimuli from either the external or the internal environment trigger the receptors sensory cells and sends afferent (sensory) neurons to the controller, the CNS, in the form of electrical impulses. Upon decision of an action the effector is the PNS, this time sending efferent (motor) neurons to perform either using the somatic (sNS) or autonomic (aNS) NS and the subsequent physiological response (Janig, 2006). In order to maintain homeostasis with regards to blood pressure (BP), the NS may need to react immediately to prevent hypotension (decrease in BP).

Sudden physical changes in body position, will require physiological reaction to maintain BP; heart activity, blood volume/viscosity and blood vessels are components needed to influence homeostasis with the NS instigating the reactions. Baroreceptors are nerves that connect the brachial and carotid arteries to the CNS informing it of stretch, with more pressure relating to more stretch (Lohmeier, 2001).

BP continuously rises and falls due to contraction (systole) and relaxation (diastole), which synchronizes with the cardiac cycle. BP is a result of cardiac output (CO) times total peripheral resistance (PR), thus when one decreases or increases BP will 5 14023982 follow suit. CO is the amount of blood pumped out of the ventricle during one minute and PR being the resistance of blood flow through the vessels dependent on diameter.

One example, stimuli stands up resulting in hypotension, glossopharyngeal and vagus nerves detect less stretch (receptor) in arteriole walls and subsequently less AP are sent to the cardiac and vasomotor centres (CC&VC) found in the medulla oblongata (Vasilenko, 2013). The CNS would send commands using the aNS to the CC (controller) to release more sympathetic impulses and less parasympathetic via baroreceptors.

Consequently the sino-atrial, atrioventricular node and cardiac muscle (effectors) are stimulated resulting in an increased heart rate and stroke volume therefore raised CO and as a result BP restores (Behnke, 2006). The VC (controller) helps restore BP, completing a negative feedback loop and homeostasis by stimulating an increase in sympathetic impulses and causing smooth muscle in arterioles to constrict (effector), vasoconstriction of the blood vessels develops thus increased PR follows suit (Coni & Coni, 2003).

Alternatively hypertension (high BP) would instigate the stages mentioned but in contrast, as parasympathetic aims to slow processes more parasympathetic impulses would be stimulated and less AP would be completed. Vessels would vasodilate, heart rate would slow resulting in a reduced BP. 6 14023982 (4) Presentation of peripheral Oedema, suffering with shortness of breath and pitting oedema, caused by heart failure. This generates fluid overload within the body and homeostatic imbalance.

Due to high hydrostatic pressure in the arteriole end of the capillary being greater than the osmatic pressure pushing the water back, fluid enters the tissues, which bathes the cells with O2 and nutrients. The issue that arises with Oedema and in this case, is continuous high hydrostatic pressure into the venous end of the capillary, superseding osmatic pressure preventing the H2O from crossing back into the capillaries to be filtered and excreted (Thornton et al, 2011).

Furosemide is a loop diuretic also known as a NKCC-inhibitor (Sodium, Potassium and Chloride) and absorbed mostly in the stomach and upper small intestine, when administered orally (Wart et al, 2013). It binds to plasma proteins, mainly albumin, binding at 91-99% in healthy individuals, reflecting its high volume of distribution of 9 litres. Some need increased albumin intake, which can be added with the drug by supplementation or via the consumption of egg whites.

Due to its weak acidic properties, it suffers a relatively short half-life of one hour and a low bioavailability of 60 and 64% oral solution and tablet form respectively, however within one hour effects are known, hitting peak production up to two hours but lasting up to eight (Sanofi-aventis, 2011). To ensure homeostasis, a negative fluid balance is first sought after, forcing the body to excrete urine in large quantities, electrolyte and the volume of urine monitored after the first dose, as a guide for strength required for the proceeding dose.

Conversely furosemide may be administered intravenously or 7 14023982 subcutaneously (Goenaga et al, 2004) for patients needing immediate medical intervention or those suffering dysphagia, this will increase bioavailability to 100% and potency, requiring monitoring in an acute setting. Once in the system furosemide is metabolised by the liver, intestine and kidneys as furosemide glucuronide (Pichette & Soulch, 1996), though due to its plasma protein binding properties, reaching the tubules via filtration is seldom and requires the organic acid transport system to be secreted and be made available.

This takes place in the kidneys, most notably in the thick ascending limb of loop of Henle. Unfortunately around 65% of said drug is excreted without use due to this processing, reflecting its low plasma concentrationsof 2-3 ? g/ml after 40mg after oral administeration (Klausner et al, 2003). Furosemide assists in the retention of the solutes Na+, K+ and 2Cl- from leaving the lumen, water will follow through its osmotic gradient to the high concentration allowing homeostasis of fluid balance to be restored.

However the loop diuretic will encourage increased excretion of Ca+ and Mg+ due to the now positively charged lumen. Excessive use may have an adverse effect and cause dehydration, blood volume reduction and electrolyte depletion. Furosemide has its downfalls such as a decline in renal function, arrhythmias and impairment of nasal mucociliary clearance (Goto et al, 2010). Furosemide is considered the gold star and last resort for fluid homeostatic imbalances due to its high potency. 8 14023982 Word count: 1991 Reference list Alharbi, N. N. S. Treagust, D. F.

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