Polycyclic Aromatic Hydrocarbons (PAHs) Research Paper - 3

Polycyclic Aromatic Hydrocarbons (PAHs) - Research Paper Example The truth is there are toxic and non-toxic PAHs occurring naturally in our environment, the non-toxic ones are found in the food we consume (Glenn 1995). They are known as Phytochemicals and are available not only in vegetables but also fruits, grains and several other plants used as foods. These are essential for our health when cooked and consumed appropriately (Sommerburg 1998). This document will discuss the benefits of consuming abundant vegetables in our diet to prevent chronic diseases. Phytochemicals are the bioactive non-nutrient compound found in vegetable. Almost 5000 phytochemicals are estimated to be identified but more are still deemed to be unknown, limiting the full knowledge of the vegetable benefits to our health, suggesting that there could be more benefits. In our day to day activities, our cells are constantly exposed to a lot of oxidizing agents, some toxic and some beneficial to our life. These are the normal PAHs and are found in air, water or the food we consume, some are even being metabolically produced within the cells. Optimal physiologic conditions in our bodies require a balanced state a balanced state of oxidants and antioxidants (Block 1992). Excessive oxidants production causes imbalance which leads to oxidative stress which mostly affects the chronic bacterial, parasitic and even viral infections. This causes serious oxidative damages to the bimolecular substances mainly the proteins, lipids and DNA increasing the risk of chronic disease s like cancer and even cardiovascular disease. Consumption of sufficient antioxidants slows down or even prevents this oxidative stress in our bodies. Vegetables are the known source to have a wide variety of these antioxidant compounds, these may be phenolics or carotenoids which helps in protecting cellular systems from damage due to the oxidative stress, reducing the risk of chronic diseases (Hung 2004). An evidence to show that the compounds found in

Is American dream dead If so should we do anything about it Essay

Is American dream dead If so should we do anything about it - Essay Example However, there are those people who believe that the American dream is dead, while others argue that the American dream is very much alive. Although none is said to be true or false, certain issues happening in the American society contradicts each other. This is the main reason for the divergent views in this motion. Initially, the American dream was concerned about creating opportunities for all Americans, opportunities that did not take into accounts either the race or nationality of people. According to the virtues of the American dream, all Americans deserve equal opportunities before the law. The idea criminalized any form of discrimination against any person due to his colour, race, religion, language, social class or nationality. Every person is entitled to equal opportunities such as job opportunities, enjoyment of rights and enjoyment of people’s freedom. The rate of unemployment in America stands at 7.60 per cent as at June of 2013 while the underemployed rate is at 14.3%. This shows that some of the Americans miss job opportunities due to different reasons. Additionally, people should have an opportunity to share in the national resources and enjoy their privileges. However, this is not the reality on the ground. Most people miss out opportunities due to their colour, race, ethnicity, language and physical looks. Since many people do not have equal opportunities, this has killed the American dream. A number of factors contributing to inequality among the American people are the main reason why the American dream is dead. Inequality, cited as the main pillar of the American dream is highly disregarded. While all Americans are supposed to pay taxes, some enjoy the rare privilege of not paying taxes. Others receive tax deductions that exempt them from paying heavy taxes. Bending of the law through various amendments now allows some people to enjoy more tax reliefs than others. Some even device crooked means of avoiding taxes. Approximately, 46.6 % of Americans do not pay income tax. Moreover, there is a huge wage gap between the rich and the poor people in the society. Approximately16 per cent of the Americans live in poverty, while 20% of the children live in abject poverty. While the rich are entitled to high salaries, the poor are poorly paid. This results in a class difference between the Americans, the rich get richer and the poor remains poorer. Payment of wages need be equal, holding all other factors constant such as level of education, experience, the type of job and the hardships encountered in the work place. Sex should not determine the amount of income that a person should receive. However, in many instances men when compared to women earn higher wages despite the fact that they hold similar positions at work. On the other hand, the American dream is still alive. Despite the cited cases of inequality, the dream is still alive among the Americans. With the high hopes and faith that we have in this dream, various people point out on the need to amend the law to make all people equal. Human rights groups and welfare organizations point out on the need to subject all Americans to a similar tax level. Other humanitarian groups such as the feminists point out that man and women require a similar pay package for similar kinds of tasks handled. Little can however be done about this problem. Despite these cases however, the dream is

Political Science Assignment Example | Topics and Well Written Essays - 250 words - 10

Political Science - Assignment Example Under the Miranda rules, the suspect has a right to contact a lawyer and if he or she cannot afford one, the federal government appoints a lawyer to represent the suspect in court. In addition, the suspect can invoke his or her right to be silent during the interrogation or demand to have an attorney before the interrogation could commence. Americans believe that the police have an obligation to inform the suspect of his or her rights. Indeed, the police read out and confirm that the suspects understand the Miranda rules read to them. The police then enquire from the suspect whether they wish to speak based on their understanding of the Miranda rules (MirandaWarning.Org, 2015). If the suspect does not understand English, the police translate and record the Miranda warning in a language convenient to the suspect. However, the police only give or read the Miranda rights and warnings to a suspect if they are facing interrogation in police custody (Thomson Reuters, 2014). Judges respect the Miranda rules and cannot use any evidence gathered from interrogations that failed to inform the suspect of their Miranda rights and warnings. Even the U.S military provides and requires suspects to sign a form that informs them of their charges and rights that protects them against self-incrimination (MirandaWarning.Org,

Final Paper Essay Example | Topics and Well Written Essays - 3750 words

Final Paper - Essay Example As society processes the information regarding the event, the victims are framed by the news media and public officials. The reaction to the event creates another class of victims as the public is penalized through loss of freedoms and privacy. Innocent people are viewed with suspicion and an unrealistic assessment of the risk places a heavy toll on a stressed society. While terrorism has existed for millennia, recent uses of the criminal act and escalated methods have increased the level of societys awareness of the victims of terrorism. There is a Chinese saying that says, "Kill one [to] frighten ten thousand" (as cited in Ewald, 2006, p.4). Where in centuries past the concept of terrorism was to instill fear, modern terrorism seeks to murder on a massive scale. It is the ability of the terrorists to murder thousands of people in a single event that evokes such fear and dread. Exploring a few of the most significant terrorist acts committed against Americans can help to understand the ways that the victims are viewed and why they become victims. They are generally victims of opportunity and symbolism. Direct victims can be viewed through the positivist lens, while the indirect victims are more aptly analyzed through the anti-positivist viewpoint. The direct victims are real and concrete, while the indirect victims are constructed through societies own labels and judgments. Killing one can indeed frighten ten thousand, and killing 3 thousand can frighten 3 million. Americans have lived with various forms of terrorism since the countrys beginning, but only recently has it been viewed as a complex social issue. Table 1 is a partial list of the most noteworthy terrorist acts in modern history. The 1993 truck bomb at the World Trade Center was the first terrorist event that took place on US soil that attracted large scale public attention. Though there had been a number of airplane hijackings throughout the previous

Instant messaging and Videoconferencing Research Paper

Instant messaging and Videoconferencing - Research Paper Example Another example is when two employees from the same department are working at distance from each other and they have to work in proper collaboration. In such situations, instant messaging is useful as they can send files to them and can talk about them in real time. The benefits of instant messaging include instantaneous response, real time messaging, and file transfer facility. Some other key features of instant messaging include perceived control and telepresence (Zaman, Anandarajan, & Dai, 2010, p. 1009). The challenges related to instant messaging include leakage of trade secrets and privacy issues. Video conferencing helps in communicating being at distance (Judge, 2010, p. 655). It can be useful at workplaces in situations where employees are located at distance from each other and they have to talk to each other frequently to discuss project related issues. Another example is when time is short and manager wants to have a meeting with his/her employees. In such situations, video conferencing is useful because it saves time and increases efficiency and productivity. The benefits of video conferencing include accessibility, utility, and flexibility (Lowden & Hostetter, 2012, p. 377). The challenges related to video conferencing include lack of training to do such interactions and lack of use of nonverbal cues during

Brutus, Antonius, Cassius, and Caesar Essay Example for Free

Brutus, Antonius, Cassius, and Caesar Essay It is 101 BC, the Roman Empire is at its zenith, and a man named Julius Caesar has the power of it within his grasp. Unwanted till now, he soon realizes the influence he now holds over so many lives. Perhaps he is naà ¯ve. However, if choosing who out of Marcus Brutus, Marcus Antonius, Cassius, and Julius Caesar; I choose whom the people chose. Julius Caesar would have been an extraordinary leader of Rome. As a revered general for the empire, he conquered many with an iron fist of trepidity including the dreaded Pompey, whose statue later, in a twisted sense of irony, Caesar meets his untimely fate upon. Caesar was a person the people of Rome could look up to, relate to, and follow. He was born and raised in Rome, joined the army at a young age and showed an almost predilectory understanding of warfare. He rose through the ranks to become the greatest general that Rome had ever known. Caesar was a remarkable man, with many kingly qualities such as his luminosity, endurance, perceptiveness, love for the people, any many, many more. He very well might have been the greatest leader that Rome would even know if not for the inequitable ideas of one man, Cassius. It was only after his return from conquering the mighty Pompey that the glory of Rome became to apparent to Julius Caesar. He wanted the crown; he wanted it like a child wants candy. With his advanced knowledge of subliminal tactics, he devised a plan that would force the citizens to beg him to take the crown. His beloved servant and yes-man, Marcus Antonius, offered him the crown three times with thousands there to witness the event; and each time Caesar refused the crown. Not because he did not want it, for he craved the crown; but because it was part of his brilliant plan. Mark Antonius speaks with anger and passion as he recounts the event of Caesars murder at his funeral, asking the people if Caesars death was truly justifiable: You all did see that on the Lupercal I thrice presented him with a kingly crown, which he did thrice refuse. Was this ambition? III: II: 102-4. At the time the event-which Anotnius gave as evidence that Caesar was not an ambitious  man, which was Brutuss only given reason for partaking in the atrocious manslaughter-Caesar showed such restraint that he had some sort of seizure on stage and was carried away by Antonius and several other men. He showed great power over himself by refusing his craving; a quality that I believe would have made him an excellent leader. Perhaps Antonius did not know of Caesars plan, which is why he spoke so highly of him. Antonius later pleaded with the people of Rome to see the truth, what truth can lie within a dishonest man such as Caesar? A man whom lied in order to persuade the citizens of Rome to make him their king. However dishonest Caesars actions might have been, he showed brilliance and patience on the Lupercal, qualities which are required for a leader, which is quite possibly why the people of Rome chose him over any other men. What ultimately led Caesar to his demise can be construed as either a positive or negative trait when put before one in different contexts. What led him to his death were both his love for Rome, and more importantly his greed. He was a man for the people, believing that he was Gods gift to them; Caesar wanted more then anything to make Rome the greatest Empire the world would ever know, yet he would stop at nothing to accomplish this. His greed would have possibly led the people of Rome into chains, forcing them to work their entire lives in order to better the empire, which is why several members of the Senate felt the need to end his plan before it began. Just after he had killed Caesar, Brutus spoke to the people attempting to explain why he had done what he felt must be done: If then that friend demand why Brutus rose against Caesar, this is my answer: Not that I loved Caesar less, but that I loved Rome more. Had you rather Caesar were living, and die all slaves, than that Caesar were dead, to live all freemen? III: II: 21-5. Brutus was right in the fact that his predictions could have very well come true, but he was wrong in assuming Caesar would not have bettered the empire for the next generation. I believe that Brutus was thinking in the right now sense, instead of tomorrow. Yes, Caesar was ambitious, and yes he was greedy, both of which are necessary qualities for a leader. Many would say that Julius Caesar would have made a horrible leader; that he was naà ¯ve, paltry, inconsiderate, pretentious, and that he had a serious  inadequacy of experience when it came to political affairs. Most would not look further then the fact that he had little experience with politics, and only see his influence to the people as a threat; a very good quality for a man in an authorial position to have, influence. I am almost certain though, that if either Brutus or Cassius had actually sat down and discussed with Caesar what his plans for the future of Rome were, they would have had a serious change of heart and mind. Caesar was a good man who had many ideas as to what an eminent empire requires. His slaughter was untimely and a grievous event which sparked a war within Rome; an event that, ironically, the conspirators had worked so hard to prevent. Caesar would have been an excellent leader of Rome because he not only refrained from making impetuous and misguided deci sions about the other characters, but he displayed selfless loyalty to the citizens of Rome and to those he loved. It is striking and shocking to think what may have happened to the world as we know it if Julius Caesar had lived, lead, and loved.

Sodium, Potassium and Urea Measurement

Sodium, Potassium and Urea Measurement Introduction Electrolytes are solutions that conduct electricity. Any molecule that becomes an ion when mixed with water is an electrolyte. Salts such as sodium, potassium, calcium and chloride are examples of electrolytes. When these molecules dissolve in water, they release ions with an electric charge, positive or negative, that attracts or repels other ions during a chemical reaction. In living cells, most chemical reaction occur in an aqueous environment since approximately 75% of the mass of the living cell is water. Normally 70kg man, represent with 42 litres of total body water that contribute for about 60% of the total body weight. (Marshall, 2000). 66% of this water is in the intracellular fluid (ICF) and 33% in the extracellular fluid (ECF). The principle univalent cations in the ECF and ICF are sodium (Na+) and potassium (K+) respectively. Sodium (Na+) Sodium is the major cation of the extracellular fluid (ECF). It represents almost one-half the osmatic strength of plasma. It plays an important role in maintaining the normal distribution of water and osmatic pressure in the ECF compartment. Sodium levels in the body are regulated ultimately by the kidneys (it excrete excess sodium). The main source of sodium is sodium chloride (NaCl- table salt) which is used in cooking. The daily requirement of the body is about 1 2 mmol/day. Sodium is filtered freely by the glomeruli. About 70 80 % of the filtered sodium load is reabsorbed actively in the proximal tubules (with chloride and water passively) and anther 20 25 % is reabsorbed in the loop of Henle (along with chloride and more water). Normal ECF sodium concentration is 135 145 mmol/L while that of the intracellular fluid (ICF) is only 4-10 mmol/L. sodium is lost via urine, sweat or stool. (Marshall, 2000). Hypernatraemia Hypernatraemia (high sodium levels in the blood) may occurs due to increase sodium intake, decrease excretion, dehydration (water loss) or failure to replace normal water losses. It can also occurs because of excessive mineral corticoid (such as Aldosterone) production acting on renal reabsorption. The clinical features of hypernatraemia are non-specific or masked by underlying conditions. Nausea, vomiting, fever and confusion may occur. A history of long standing polyuria, polydipsia, and theist indicates diabetes insipidus. Hypernatraemia is caused by many diseases such as renal failure, Cushings syndrome or Conns syndrome. Conns syndrome is a disease of the adrenal glands involving excess production of a hormone, called aldosterone. Another name for the condition is primary hyperaldosteronism. Hyponatraemia Hyponatraemia (low sodium levels in the blood) is caused by impaired renal reabsorption of sodium. This occurs in Addisons disease of the adrenal gland due to loss of aldosterone producing zona glomerulosa cortical cells. Sodium decreases in severe sweating in a hot climate or during physical exertion such as marathon running. Falsely low serum sodium concentration may be found in hyperlipidaemic states where the sodium concentration in the aqueous phase of the serum is actually normal, but the lipid contributes to the total volume of serum measured. The symptoms are non-specific and include headache, confusion and restlessness. Hyponatraemia is seen in Addisons disease and/or excessive diuretic therapy. (Kumar Clark, 2002) Potassium (K+) It is the major intracellular cation. It is average concentration in tissue cells is 150mmol/L and in RBCs is 105 mmol/L. The body requirement for K+ is satisfied by a dietary intake. K+ is absorbed by the gastrointestinal tract and distributed rapidly, with a small amount taken up by cells and most excreted by the kidneys. Potassium which filtered by the glomeruli is reabsorbed almost completely in the proximal tubules (PT) and then secreted in the distal tubules (DT) in exchange for sodium under the influence of aldosterone. Factors that regulate distal tubular secretion of potassium include intake of sodium and potassium, water flow rate in distal tubules, plasma level of mineralocorticoids, and acid-base balance. Renal tubular acidosis, as well as metabolic and respiratory acidosis and alkalosis also affect renal regulation of potassium excretion. (Kumar Clark, 2002). Hyperkalaemia Hyperkalaemia is high K+ levels in the blood. Potassium is in high concentration within cells than in extracellular fluids. This means that relatively small changes in plasma concentration can underestimate possibly larger changes in intracellular concentrations. In addition, extensive tissue necrosis can liberate large amounts of potassium into the plasma causing the concentration to reach dangerously high levels. The commonest cause of hyperkalaemia is kidney failure causing decreased urinary potassium excretion. Severe hyperkalaemia (> 6.5 mmol/l) is a serious medical emergency needs treatment as fast as possible because of the risk of developing cardiac arrest. Moderate hyperkalaemia is relatively asymptomatic emphasising the importance of regular biochemical monitoring to avoid sudden fatal complications Hypokalaemia Hypokalaemia (low potassium levels in the blood) has many causes; the most common are diuretic treatment (particularly thiazides), hyperaldosteronism and renal disease. Hypokalaemia is often associated with a metabolic alkalosis due to hydrogen ion shift into the intracellular compartment. Clinically, it presents with paralysis, muscular weakness and cardiac dysrhythmais. (Kumar Clark, 2002) Aldosterone Aldosterone is a steroidal hormone secreted by the adrenal cortex. It is the hormone that regulates the bodys electrolyte balance. This hormone synthesized exclusively in the zona glomerulosa region of the adrenal cortex. This zona contains 18-hydroxysteroid dehydrogenase enzyme which a requisite enzyme for the formation of Aldosterone. Aldosterone acts directly on the kidney tubules to decrease the secretion rate of sodium ion (with accompanying retention of water), and to increase the excretion rate of potassium ion. The secretion of aldosterone is regulated by two mechanisms. First, the concentration of sodium ions secreted may be a factor since increased rates of aldosterone secretion are found when dietary sodium is severely limited. Second, reduced blood flow to the kidney stimulates certain kidney cells to secrete the proteolytic enzyme renin, which converts the inactive angiotensinogen globulin in the blood into angiotensin 1. Another enzyme then converts angiotensin I into a ngiotensin II, its active form. This peptide, in turn, stimulates the secretion of aldosterone by the adrenal cortex. Pathologically elevated aldosterone secretion with concomitant excessive retention of salt and water often results in edema. (Kumar Clark, 2002) Urea is a by-product of protein metabolism that is formed in the liver is formed by the enzymatic deamination of amino acids (urea cycle). The immediate precursor of urea is arginine, which is hydrolyzed to give urea and Ornithine. The urea is excreted by the kidneys and Ornithine in the liver combine with ammonia, formed by the catabolism of amino acids, to regenerate arginine and thereby continue the process of urea formation. The blood urea nitrogen (BUN) test measures the level of urea nitrogen in a sample of the patients blood. In healthy people, most urea nitrogen is filtered out by the kidneys and leaves the body in the urine, because urea contains ammonia, which is toxic to the body. If the patients kidneys are not functioning properly or if the body is using large amounts of protein, the BUN level will rise. If the patient has severe liver disease, the BUN will drop. High levels of BUN may indicate kidney disease or failure; blockage of the urinary tract by a kidney stone or tumour; a heart attack or congestive heart failure; dehydration; fever; shock; or bleeding in the digestive tract. High BUN levels can sometimes occur during late pregnancy or result from eating large amounts of protein-rich foods. A BUN level higher than 100 mg/dl, points to severe kidney damage. (Kumar Clark, 2002) Materials and method Please refer to medical biochemistry practical book (BMS2). Result The equation obtained from the graph used to calculate the Urea concentration of patients is: Y = 0.0238 X Where Y = absorbance X = urea concentration Patient 1 = 0.231/0.0238 = 9.7 mmol/L Patient 2 = 0.149/0.0238 = 6.3 mmol/L Patient 3 = 0.188/0.0238 = 7.89 x 10 = 78.9 mmol/L Patient 4 = 0.376/0.0238 = 7.5 mmol/L Discussion The concentration of sodium and potassium for the four patients was measured by using the flame photometer. For the estimation of urea concentration, a standard calibration curve using different standard concentrations been plotted which used to determine the test samples concentrations. In this practical, the abnormal conditions are varying for each of the patients. Addisons disease is a disorder of the adrenal cortex in which the adrenal glands are under active, resulting in a deficiency of adrenal hormones. Addisons disease can start at any age and affects males and females equally. The adrenal glands are affected by an autoimmune reaction in which the bodys immune system attacks and destroys the adrenal cortex. The glands may also be destroyed by cancer, an infection such as tuberculosis, or another identifiable disease. In infants and children, Addisons disease may be due to a genetic abnormality of the adrenal glands. The majority of the clinical features of adrenal failure are due to lack of glucocorticoid and mineralcorticoid. In Addisons disease cortisol levels are reduced which lead, through feedback, to increase corticotrophin-releasing hormone (CRH) and adrenocorticotrophic hormone (ACTH) production. When the adrenal glands become under active, they tend to produce inadequate amounts of all adrenal hormones. Thus, Addisons disease aff ects the balance of water, sodium, and potassium in the body, as well as the bodys ability to control blood pressure and react to stress. In addition, loss of androgens, such as dehydroepiandrosterone (DHEA), may cause a loss of the body hair in women. A deficiency of aldosterone in particular causes the body to excrete large amount of sodium and potassium, leading to low levels of sodium and high levels of potassium in the blood. The kidneys are not able to concentrate urine, so when a person with Addisons disease drinks too much water or loses too much sodium, the level of sodium in the blood falls. Inability to concentrate urine ultimately causes the person to urinate excessively and become dehydrated. Severe dehydration and low sodium level reduce blood volume and can culminate in shock. Dehydration also causes a high blood urea level. In Addisons disease, the pituitary gland produces more corticotrophin in an attempt to stimulate the adrenal glands. Corticotrophin also stimulat es melanin production, so dark pigmentation of the skin and the lining of the mouth often develop. People with Addisons disease are not able to produce additional corticosteroids when they are stressed. Therefore, they are susceptible to serious symptoms and complications when confronted with illness, extreme fatigue, severe injury, surgery, or possibly severe psychological stress. Secondary adrenal insufficiency is a term given to a disorder that resembles Addisons disease. In this disorder, the adrenal glands are under active because the pituitary gland is not stimulating them, not because the adrenal glands have been destroyed. Blood tests may show low sodium level and high potassium level and usually indicate that the kidneys are not working well. The cortisol level may be low and corticotrophin level may be high. However, the diagnosis is usually confirmed by measuring cortisol level after they have been stimulated with corticotrophin. If cortisol level is low, further tests are needed to determine if problem is Addisons or secondary adrenal insufficiency. Patient-1 has very low sodium 116 mmol/L (135-145 mmol/L), high potassium 6.2 mmol/L (3.6-5.0 mmol/L) and high urea 9.7 mmol/L (3.3-7.5 mmol/L). These abnormal results mostly fit Addisons disease. Sodium been lost in urine in exchange with potassium which causes depletion of Na+ in the blood and increase K+ as both cortisol and aldesterone hormones are absent. Urea level is elevated as a secondary to dehydration and could be due to renal perfusion. ACTH measurement can be used to confirm the diagnosis. Conns syndrome is known as primary aldostronism, is due to the hyper secretion of aldesterone, usually by adenoma of the adrenal cortex or loss often nodular hyperplasia. It characterised by sodium retention and potassium depletion, because plasma renin feed back mechanism is depressed. Under normal conditions aldesterone is regulated by the renin angiotensim mechanism. The principle physiological function of aldesterone is to conserve Na+ . It dose this mainly by facilitating the reabsorption of Na+ and excretion of K+ and H+ in the distal renal tubule. Aldesterone also plays a major role in regulating water and electrolytes balance and blood pressure. The renin-angiotension aldesterone system is the most important controlling mechanism, but ACTH, Na+ and K+ also affect aldesterone secretion. The release of the enzyme renin is stimulated by fall in circulating blood volume or renal perfusion pressure and loss of Na+. The enzyme stimulate the osmoreceptors in the hypothalamus which c auses the release of antidiuretic hormone (ADH) from posterior pituitary gland. ADH targets the kidneys to increase the water reabsorption and causes arterioles to constrict. Renin also acts on its substrate and splits off the inactive decapeptide angiotensim I. Then angiotenism-converting enzyme (ACE), present in lung and plasma, converts angiotensim I to the active angiotensim II which stimulates the release of aldesterone by the adrenal cortex. Aldosterone increases the retention of sodium, chloride ions and water by the kidneys. The laboratory findings include low serum potassium which is a consequence of increased renal potassium excretion, normal or slightly increased sodium in plasma due to increased reabsorption from the renal tubules. Also the renin level will be low and do not rise in response to sodium depletion as they would be in normal persons. In addition, prolonged potassium depletion and hypertension are signs of renal damage. The clinical significance of Coons disease represented with hypertension, muscular weakness and anther neurological manifestation due to loss of K+ which play role in muscles and neurons contraction. Polyuria and thirst secondary to poor renal concentration. Any patient represent hypertension with low potassium concentration should be suspected to have Coons disease. Any patient under diuretic treatment should be monitored overnight as this manifest low potassium. Patient-2 has normal urea level 6.3 mmol/L (3.3-7.5 mmol/L), sodium result is 144 mmol/L, just below the upper limit (135-145 mmol/L) and very low potassium which supports the diagnosis of Coons syndrome. The high aldosterone level in the blood acts on the kidneys to increase the loss of mineral potassium in the urine and facilitate the reabsorption of Na+. Renal failure is the inability of the kidneys to adequately filter metabolic waste products from the blood. Chronic kidney failure is a gradual decline in kidney function which may be explained in terms of a full solute load fall in on a reduced number of functionally normal nephrons. The glomerular filtration rate (GFR) is invariably reduced, associated with retention of urea, creatinine, urate and other organic substances. The kidneys are less able to control the amount and distribution of body water (fluid balance) and the levels of electrolytes (sodium, potassium, calcium, phosphate) in the blood and blood pressure often rise. The kidneys lose their ability to produce sufficient amounts of a hormone (erythropoietin) that stimulates the formation of new red blood cells, resulting in a low red blood cell count (anemia). In children, kidney failure affects the growth of bones. In both children and adults, kidney failure can lead to weaker, abnormal bones. The increased solute load per nephrons impairs the kidneys ability to reduce concentrated urine. As the GFR falls to lower levels retention of Na+ occurs but there is no consistent pattern alteration in plasma Na+ in these cases and in many the results remain normal. Potassium clearance may be increased and raised plasma K+ is uncommon in spite of the tendency for K+ to come out of cells due to the metabolic acidosis that is usually present. However, patients with renal failure are unable to excrete large loads of K+. The level of urea and creatinine will also rise as a result of decreased excretion by the kidneys. Patient-3 has a normal sodium levels 137 mmol/L with a high potassium .8.7 mmol/L and very high urea (78.9 mmol/l) levels which indicates abnormal kidney function. The patient is most probably suffering from chronic renal failure. The numbers of healthy functioning normal nephrons are reduced therefore; there will be a reduction in the execration of urea which will accumulates in the blood. Because of the low GRF, potassium blood levels are increased. The patient must undergo renal dialysis. Diabetic ketoacidosis (DKA) is a common acute complication of insulin-dependent, or type 1 diabetes mellitus (IDDM) due to insulin deficiency which is accompanied by raised plasma concentration of diabetogenic hormones (Adrenaline, Cortisol, Growth hormone and Glucagon ).Before the discovery of insulin in the 1920s, patients rarely survived diabetic ketoacidosis. This complication is still potentially lethal, with an average mortality rate between 5 and 10%. Although the risk of diabetic ketoacidosis is greatest for patients with IDDM, the condition may also occur in patients with non- insulin-dependent diabetes (NIDDM) under stressful conditions, such as during a myocardial infarction. Common symptoms are thirst due to dehydration, polyuria, nausea and weakness that have progressed over several days, which result in coma over the course of several hours. Because of the variable symptoms, diabetic ketoacidosis should be considered in any ill diabetic patient, particularly if the patient presents with nausea and vomiting. Common clinical findings include tachycardia, tachypnea, dehydration, altered mental status and a fruity breath odour, indicating the presence of ketones. Plasma glucose is normally maintained between 4.5 and 8.0mmol/1. Without insulin, most cells cannot use the sugar that is in the blood. Cells still need energy to survive, and they switch to a back-up mechanism to obtain energy. Fat cells begin to break down, producing compounds called ketones. Ketones provide some energy to cells but also make the blood too acidic (ketoacidosis). Since plasma glucose diabetic ketoacidosis exceed the renal threshold; glucose is always present in the urine of patients (glycosuria) with ketoacidosis, the pH of the blood is important in determining the severity of the condition. Blood normally has a pH of 7.35-7.45, maintained by the buffering systems, the most important of which is the bicarbonate buffer system. When acids accumulate in the blood, they dissociate with an increase in hydrogen ion concentration. Bicarbonate can usually neutralise hydrogen ions by incorporating them into water. DKA is associated with electrolyte imbalances; sodium and potassium levels in particular are affected. Serum sodium levels may be low, high or normal. When evaluating the serum sodium level, it is helpful to remember that hyperglycemia causes a shift of free water into the extracellular space, diluting the measured sodium concentration which results in lost of sodium via lie urine as a result of osmotic diuresis. In addition, vomiting, a common feature of ketoacidosis is associated with a loss of sodium from the gastrointestinal tract. This might not always be reflected in the blood results because it is a measure of concentration and, as has already been illustrated, dehydration will be present. Normal plasma sodium levels are maintained between 135 and 145mmol/l, however, despite the actual deficit, patients with DKA might display wide-ranging plasma sodium levels depending on the relative losses of water and sodium. Total body potassium is always depleted in ketoacidosis as potassium is also lost in urine and vomit. The plasma concentration of potassium, however, remains relatively high due to the passage of potassium out of the cells and into the extracellular fluid. One of the mechanisms that normally control the passage of potassium into and out of cells is the sodium/potassium pump. This pump requires intracellular glucose, which is not available in ketoacidosis, consequently, the pump cannot function and potassium leaks out of the cell and into the plasma. Furthermore, potassium is freely exchangeable with hydrogen across the cell membrane. If the hydrogen concentration is high as in DKA, hydrogen will move into the cell in exchange for potassium. So, despite an overall potassium deficit, plasma levels are usually raised in ketoacidosis, at the expense of the body cells. The kidneys can malfunction, resulting in kidney failure that may require dialysis or kidney transplantation. Doctors usu ally check the urine of people with diabetes for abnormally high levels of protein (albumin), which is an early sign of kidney damage. At the earliest sign of kidney complications, the person is often given angiotensin-converting enzyme (ACE) inhibitors, drugs that slow the progression of kidney disease by decreasing blood flow to the kidneys which prevent the kidneys from excreting normal amounts of potassium leads to mild hyperkalaemia. The result obtained for patient-4 corresponding with the clinical findings found in diabetic ketoacidosis. The sodium is reduced (130 mmol/L) and the potassium reading is relatively high (5.8 mmol/L) when compared with the normal reference range. There is a marked increase in urea (15.6 mmol/L) because as mentioned earlier the kidneys can malfunction, resulting in kidney failure that will concentrate fluid in the extracellular compartment. Conclusion Patient 1 is suffering from Addisons disease Patient 2 is suffering from Coons syndrome Patient 3 is suffering from chronic renal failure Patient 4 is suffering from diabetic ketoacidos Questions Calculate the osmolarity (mmol/L) for each patient. Why would patients3s (the diabetic) osmolarity be underestimate? Osmolarity is a property of particles of solute per liter of solution. If a substance can dissociate in solution, it may contribute more than one equivalent to the osmolarity of the solution. The expected osmolarity of plasma can be calculated according to the following formula. Calculated osmolarity (mOsm/kg) = 2*[Na +] + 2*[K+] + (glucose) + (urea) Patient 1 = 2 x 116 + 2 x 6.2 + [glucose] + 9.7 Patient 2 = 2 x 144 + 2 x 2.8 + [glucose] + 6.3 Patient 3 = 2 x 137 + 2 x 8.7 + [glucose] + 78.9 Patient 4 = 2 x 130 + 2 x 5.8 + [glucose] + 15.7 The final result is not obtained as the glucose values are not given, so the calculation can not be done without glucose values. The patient 3 (the diabetic) osmolarity is underestimated because of insulin deficiency, the cells uptake of glucose, which causes hyperglycaemia. What is the abnormality in the clinical condition Diabetes Insipidus, and how does it affect water electrolyte balance? Many different hormones help to control metabolic activities within the body. One of these is called anti-diuretic hormone (ADH) and its function is to help control the balance of water in the body. It does this by regulating the production of urine. ADH is produced by the hypothalamus and then stored in the pituitary gland until it is needed. Diabetes Insipidus usually results from the decreased production of antidiuretic hormone. Alternatively, the disorder may be caused by failure of the pituitary gland to release Antidiuretic hormone into the bloodstream. Other causes of diabetes Insipidus include damage done during surgery on the hypothalamus or pituitary gland; a brain injury, particularly a fracture of the base of the skull; a tumor; sarcoidosis or tuberculosis; an aneurysm (a bulge in the wall of an artery) or blockage in the arteries leading to the brain; some forms of encephalitis or meningitis; and the rare disease Langerhans cell granulomatosis (histiocytosis X). Another type of diabetes Insipidus, nephrogenic diabetes Insipidus, may be caused by abnormalities in the kidneys. Diabetes Insipidus suspected in people who produce large amounts of urine. They first test the urine for sugar to rule out diabetes mellitus. Blood tests show abnormal levels of many electrolytes, including a high level of sodium. The best test is a water deprivation test, in which urine production, blood electrolyte (sodium) levels, and weight are measured regularly for a period of about 12 hours, during which the person is not allowed to drink. A doctor monitors the persons condition throughout the course of the test. At the end of the 12 hours, or sooner if the persons blood pressure falls or heart rate increases or if he loses more than 5% of his body weight, the doctor stops the test and injects Antidiuretic hormone. The diagnosis of central diabetes Insipidus is confirmed if, in response to Antidiuretic hormone, the persons excessive urination stops, the urine becomes mor e concentrated, the blood pressure rises, and the heart beats more normally. The diagnosis of nephrogenic diabetes Insipidus is made if, after the injection, the excessive urination continues, the urine remains dilute, and blood pressure and heart rate do not change. How do diuretics work? And what are the three main groups of diuretics? Diuretics work in the kidneys to increase the elimination of water and electrolytes, thereby causing more urine to form. Because the amount of fluid in the body is lowered, blood pressure goes down, too. Different chemical types work in different areas of the nephrons; so many different classes of diuretics are used. Three of the most common classes of diuretics are: Thiazide and Thiazide-Like Diuretics Drugs containing the chemical Thiazide and similar chemicals like indapamide and metolazone are suggested as the first drugs to try for most people with high blood pressure. They affect the distal convoluted tubule, where large amounts of sodium and water are absorbed back into the body. By blocking the re-absorption process, these drugs force more sodium and more water into the urine to be removed from the body. Thiazides may also relax the muscles in blood vessel walls, making blood flow more easily. Loop Diuretics More powerful than the Thiazide are classes of diuretics that work in the area of the Loop of Henle. These loop diuretics mainly interfere with the bodys re-absorption of chloride, but they also keep sodium from re-entering the blood. Unfortunately, loop diuretics are also more likely to promote the elimination of calcium, magnesium and especially potassium. Shortages of any of these essential electrolytes can cause serious problems such as irregular heartbeats. Potassium-Sparing Diuretics The third common group of diuretics consists of drugs that are much weaker than the Thiazides or the loop diuretics but potassium-sparing diuretics do not reduce potassium levels nearly as much as other kinds of diuretics do. They inhibit aldosterone and/or block sodium reabsorption and inhibit potassium excretion in the distal tubule. Sodium, Potassium and Urea Measurement Sodium, Potassium and Urea Measurement Introduction Electrolytes are solutions that conduct electricity. Any molecule that becomes an ion when mixed with water is an electrolyte. Salts such as sodium, potassium, calcium and chloride are examples of electrolytes. When these molecules dissolve in water, they release ions with an electric charge, positive or negative, that attracts or repels other ions during a chemical reaction. In living cells, most chemical reaction occur in an aqueous environment since approximately 75% of the mass of the living cell is water. Normally 70kg man, represent with 42 litres of total body water that contribute for about 60% of the total body weight. (Marshall, 2000). 66% of this water is in the intracellular fluid (ICF) and 33% in the extracellular fluid (ECF). The principle univalent cations in the ECF and ICF are sodium (Na+) and potassium (K+) respectively. Sodium (Na+) Sodium is the major cation of the extracellular fluid (ECF). It represents almost one-half the osmatic strength of plasma. It plays an important role in maintaining the normal distribution of water and osmatic pressure in the ECF compartment. Sodium levels in the body are regulated ultimately by the kidneys (it excrete excess sodium). The main source of sodium is sodium chloride (NaCl- table salt) which is used in cooking. The daily requirement of the body is about 1 2 mmol/day. Sodium is filtered freely by the glomeruli. About 70 80 % of the filtered sodium load is reabsorbed actively in the proximal tubules (with chloride and water passively) and anther 20 25 % is reabsorbed in the loop of Henle (along with chloride and more water). Normal ECF sodium concentration is 135 145 mmol/L while that of the intracellular fluid (ICF) is only 4-10 mmol/L. sodium is lost via urine, sweat or stool. (Marshall, 2000). Hypernatraemia Hypernatraemia (high sodium levels in the blood) may occurs due to increase sodium intake, decrease excretion, dehydration (water loss) or failure to replace normal water losses. It can also occurs because of excessive mineral corticoid (such as Aldosterone) production acting on renal reabsorption. The clinical features of hypernatraemia are non-specific or masked by underlying conditions. Nausea, vomiting, fever and confusion may occur. A history of long standing polyuria, polydipsia, and theist indicates diabetes insipidus. Hypernatraemia is caused by many diseases such as renal failure, Cushings syndrome or Conns syndrome. Conns syndrome is a disease of the adrenal glands involving excess production of a hormone, called aldosterone. Another name for the condition is primary hyperaldosteronism. Hyponatraemia Hyponatraemia (low sodium levels in the blood) is caused by impaired renal reabsorption of sodium. This occurs in Addisons disease of the adrenal gland due to loss of aldosterone producing zona glomerulosa cortical cells. Sodium decreases in severe sweating in a hot climate or during physical exertion such as marathon running. Falsely low serum sodium concentration may be found in hyperlipidaemic states where the sodium concentration in the aqueous phase of the serum is actually normal, but the lipid contributes to the total volume of serum measured. The symptoms are non-specific and include headache, confusion and restlessness. Hyponatraemia is seen in Addisons disease and/or excessive diuretic therapy. (Kumar Clark, 2002) Potassium (K+) It is the major intracellular cation. It is average concentration in tissue cells is 150mmol/L and in RBCs is 105 mmol/L. The body requirement for K+ is satisfied by a dietary intake. K+ is absorbed by the gastrointestinal tract and distributed rapidly, with a small amount taken up by cells and most excreted by the kidneys. Potassium which filtered by the glomeruli is reabsorbed almost completely in the proximal tubules (PT) and then secreted in the distal tubules (DT) in exchange for sodium under the influence of aldosterone. Factors that regulate distal tubular secretion of potassium include intake of sodium and potassium, water flow rate in distal tubules, plasma level of mineralocorticoids, and acid-base balance. Renal tubular acidosis, as well as metabolic and respiratory acidosis and alkalosis also affect renal regulation of potassium excretion. (Kumar Clark, 2002). Hyperkalaemia Hyperkalaemia is high K+ levels in the blood. Potassium is in high concentration within cells than in extracellular fluids. This means that relatively small changes in plasma concentration can underestimate possibly larger changes in intracellular concentrations. In addition, extensive tissue necrosis can liberate large amounts of potassium into the plasma causing the concentration to reach dangerously high levels. The commonest cause of hyperkalaemia is kidney failure causing decreased urinary potassium excretion. Severe hyperkalaemia (> 6.5 mmol/l) is a serious medical emergency needs treatment as fast as possible because of the risk of developing cardiac arrest. Moderate hyperkalaemia is relatively asymptomatic emphasising the importance of regular biochemical monitoring to avoid sudden fatal complications Hypokalaemia Hypokalaemia (low potassium levels in the blood) has many causes; the most common are diuretic treatment (particularly thiazides), hyperaldosteronism and renal disease. Hypokalaemia is often associated with a metabolic alkalosis due to hydrogen ion shift into the intracellular compartment. Clinically, it presents with paralysis, muscular weakness and cardiac dysrhythmais. (Kumar Clark, 2002) Aldosterone Aldosterone is a steroidal hormone secreted by the adrenal cortex. It is the hormone that regulates the bodys electrolyte balance. This hormone synthesized exclusively in the zona glomerulosa region of the adrenal cortex. This zona contains 18-hydroxysteroid dehydrogenase enzyme which a requisite enzyme for the formation of Aldosterone. Aldosterone acts directly on the kidney tubules to decrease the secretion rate of sodium ion (with accompanying retention of water), and to increase the excretion rate of potassium ion. The secretion of aldosterone is regulated by two mechanisms. First, the concentration of sodium ions secreted may be a factor since increased rates of aldosterone secretion are found when dietary sodium is severely limited. Second, reduced blood flow to the kidney stimulates certain kidney cells to secrete the proteolytic enzyme renin, which converts the inactive angiotensinogen globulin in the blood into angiotensin 1. Another enzyme then converts angiotensin I into a ngiotensin II, its active form. This peptide, in turn, stimulates the secretion of aldosterone by the adrenal cortex. Pathologically elevated aldosterone secretion with concomitant excessive retention of salt and water often results in edema. (Kumar Clark, 2002) Urea is a by-product of protein metabolism that is formed in the liver is formed by the enzymatic deamination of amino acids (urea cycle). The immediate precursor of urea is arginine, which is hydrolyzed to give urea and Ornithine. The urea is excreted by the kidneys and Ornithine in the liver combine with ammonia, formed by the catabolism of amino acids, to regenerate arginine and thereby continue the process of urea formation. The blood urea nitrogen (BUN) test measures the level of urea nitrogen in a sample of the patients blood. In healthy people, most urea nitrogen is filtered out by the kidneys and leaves the body in the urine, because urea contains ammonia, which is toxic to the body. If the patients kidneys are not functioning properly or if the body is using large amounts of protein, the BUN level will rise. If the patient has severe liver disease, the BUN will drop. High levels of BUN may indicate kidney disease or failure; blockage of the urinary tract by a kidney stone or tumour; a heart attack or congestive heart failure; dehydration; fever; shock; or bleeding in the digestive tract. High BUN levels can sometimes occur during late pregnancy or result from eating large amounts of protein-rich foods. A BUN level higher than 100 mg/dl, points to severe kidney damage. (Kumar Clark, 2002) Materials and method Please refer to medical biochemistry practical book (BMS2). Result The equation obtained from the graph used to calculate the Urea concentration of patients is: Y = 0.0238 X Where Y = absorbance X = urea concentration Patient 1 = 0.231/0.0238 = 9.7 mmol/L Patient 2 = 0.149/0.0238 = 6.3 mmol/L Patient 3 = 0.188/0.0238 = 7.89 x 10 = 78.9 mmol/L Patient 4 = 0.376/0.0238 = 7.5 mmol/L Discussion The concentration of sodium and potassium for the four patients was measured by using the flame photometer. For the estimation of urea concentration, a standard calibration curve using different standard concentrations been plotted which used to determine the test samples concentrations. In this practical, the abnormal conditions are varying for each of the patients. Addisons disease is a disorder of the adrenal cortex in which the adrenal glands are under active, resulting in a deficiency of adrenal hormones. Addisons disease can start at any age and affects males and females equally. The adrenal glands are affected by an autoimmune reaction in which the bodys immune system attacks and destroys the adrenal cortex. The glands may also be destroyed by cancer, an infection such as tuberculosis, or another identifiable disease. In infants and children, Addisons disease may be due to a genetic abnormality of the adrenal glands. The majority of the clinical features of adrenal failure are due to lack of glucocorticoid and mineralcorticoid. In Addisons disease cortisol levels are reduced which lead, through feedback, to increase corticotrophin-releasing hormone (CRH) and adrenocorticotrophic hormone (ACTH) production. When the adrenal glands become under active, they tend to produce inadequate amounts of all adrenal hormones. Thus, Addisons disease aff ects the balance of water, sodium, and potassium in the body, as well as the bodys ability to control blood pressure and react to stress. In addition, loss of androgens, such as dehydroepiandrosterone (DHEA), may cause a loss of the body hair in women. A deficiency of aldosterone in particular causes the body to excrete large amount of sodium and potassium, leading to low levels of sodium and high levels of potassium in the blood. The kidneys are not able to concentrate urine, so when a person with Addisons disease drinks too much water or loses too much sodium, the level of sodium in the blood falls. Inability to concentrate urine ultimately causes the person to urinate excessively and become dehydrated. Severe dehydration and low sodium level reduce blood volume and can culminate in shock. Dehydration also causes a high blood urea level. In Addisons disease, the pituitary gland produces more corticotrophin in an attempt to stimulate the adrenal glands. Corticotrophin also stimulat es melanin production, so dark pigmentation of the skin and the lining of the mouth often develop. People with Addisons disease are not able to produce additional corticosteroids when they are stressed. Therefore, they are susceptible to serious symptoms and complications when confronted with illness, extreme fatigue, severe injury, surgery, or possibly severe psychological stress. Secondary adrenal insufficiency is a term given to a disorder that resembles Addisons disease. In this disorder, the adrenal glands are under active because the pituitary gland is not stimulating them, not because the adrenal glands have been destroyed. Blood tests may show low sodium level and high potassium level and usually indicate that the kidneys are not working well. The cortisol level may be low and corticotrophin level may be high. However, the diagnosis is usually confirmed by measuring cortisol level after they have been stimulated with corticotrophin. If cortisol level is low, further tests are needed to determine if problem is Addisons or secondary adrenal insufficiency. Patient-1 has very low sodium 116 mmol/L (135-145 mmol/L), high potassium 6.2 mmol/L (3.6-5.0 mmol/L) and high urea 9.7 mmol/L (3.3-7.5 mmol/L). These abnormal results mostly fit Addisons disease. Sodium been lost in urine in exchange with potassium which causes depletion of Na+ in the blood and increase K+ as both cortisol and aldesterone hormones are absent. Urea level is elevated as a secondary to dehydration and could be due to renal perfusion. ACTH measurement can be used to confirm the diagnosis. Conns syndrome is known as primary aldostronism, is due to the hyper secretion of aldesterone, usually by adenoma of the adrenal cortex or loss often nodular hyperplasia. It characterised by sodium retention and potassium depletion, because plasma renin feed back mechanism is depressed. Under normal conditions aldesterone is regulated by the renin angiotensim mechanism. The principle physiological function of aldesterone is to conserve Na+ . It dose this mainly by facilitating the reabsorption of Na+ and excretion of K+ and H+ in the distal renal tubule. Aldesterone also plays a major role in regulating water and electrolytes balance and blood pressure. The renin-angiotension aldesterone system is the most important controlling mechanism, but ACTH, Na+ and K+ also affect aldesterone secretion. The release of the enzyme renin is stimulated by fall in circulating blood volume or renal perfusion pressure and loss of Na+. The enzyme stimulate the osmoreceptors in the hypothalamus which c auses the release of antidiuretic hormone (ADH) from posterior pituitary gland. ADH targets the kidneys to increase the water reabsorption and causes arterioles to constrict. Renin also acts on its substrate and splits off the inactive decapeptide angiotensim I. Then angiotenism-converting enzyme (ACE), present in lung and plasma, converts angiotensim I to the active angiotensim II which stimulates the release of aldesterone by the adrenal cortex. Aldosterone increases the retention of sodium, chloride ions and water by the kidneys. The laboratory findings include low serum potassium which is a consequence of increased renal potassium excretion, normal or slightly increased sodium in plasma due to increased reabsorption from the renal tubules. Also the renin level will be low and do not rise in response to sodium depletion as they would be in normal persons. In addition, prolonged potassium depletion and hypertension are signs of renal damage. The clinical significance of Coons disease represented with hypertension, muscular weakness and anther neurological manifestation due to loss of K+ which play role in muscles and neurons contraction. Polyuria and thirst secondary to poor renal concentration. Any patient represent hypertension with low potassium concentration should be suspected to have Coons disease. Any patient under diuretic treatment should be monitored overnight as this manifest low potassium. Patient-2 has normal urea level 6.3 mmol/L (3.3-7.5 mmol/L), sodium result is 144 mmol/L, just below the upper limit (135-145 mmol/L) and very low potassium which supports the diagnosis of Coons syndrome. The high aldosterone level in the blood acts on the kidneys to increase the loss of mineral potassium in the urine and facilitate the reabsorption of Na+. Renal failure is the inability of the kidneys to adequately filter metabolic waste products from the blood. Chronic kidney failure is a gradual decline in kidney function which may be explained in terms of a full solute load fall in on a reduced number of functionally normal nephrons. The glomerular filtration rate (GFR) is invariably reduced, associated with retention of urea, creatinine, urate and other organic substances. The kidneys are less able to control the amount and distribution of body water (fluid balance) and the levels of electrolytes (sodium, potassium, calcium, phosphate) in the blood and blood pressure often rise. The kidneys lose their ability to produce sufficient amounts of a hormone (erythropoietin) that stimulates the formation of new red blood cells, resulting in a low red blood cell count (anemia). In children, kidney failure affects the growth of bones. In both children and adults, kidney failure can lead to weaker, abnormal bones. The increased solute load per nephrons impairs the kidneys ability to reduce concentrated urine. As the GFR falls to lower levels retention of Na+ occurs but there is no consistent pattern alteration in plasma Na+ in these cases and in many the results remain normal. Potassium clearance may be increased and raised plasma K+ is uncommon in spite of the tendency for K+ to come out of cells due to the metabolic acidosis that is usually present. However, patients with renal failure are unable to excrete large loads of K+. The level of urea and creatinine will also rise as a result of decreased excretion by the kidneys. Patient-3 has a normal sodium levels 137 mmol/L with a high potassium .8.7 mmol/L and very high urea (78.9 mmol/l) levels which indicates abnormal kidney function. The patient is most probably suffering from chronic renal failure. The numbers of healthy functioning normal nephrons are reduced therefore; there will be a reduction in the execration of urea which will accumulates in the blood. Because of the low GRF, potassium blood levels are increased. The patient must undergo renal dialysis. Diabetic ketoacidosis (DKA) is a common acute complication of insulin-dependent, or type 1 diabetes mellitus (IDDM) due to insulin deficiency which is accompanied by raised plasma concentration of diabetogenic hormones (Adrenaline, Cortisol, Growth hormone and Glucagon ).Before the discovery of insulin in the 1920s, patients rarely survived diabetic ketoacidosis. This complication is still potentially lethal, with an average mortality rate between 5 and 10%. Although the risk of diabetic ketoacidosis is greatest for patients with IDDM, the condition may also occur in patients with non- insulin-dependent diabetes (NIDDM) under stressful conditions, such as during a myocardial infarction. Common symptoms are thirst due to dehydration, polyuria, nausea and weakness that have progressed over several days, which result in coma over the course of several hours. Because of the variable symptoms, diabetic ketoacidosis should be considered in any ill diabetic patient, particularly if the patient presents with nausea and vomiting. Common clinical findings include tachycardia, tachypnea, dehydration, altered mental status and a fruity breath odour, indicating the presence of ketones. Plasma glucose is normally maintained between 4.5 and 8.0mmol/1. Without insulin, most cells cannot use the sugar that is in the blood. Cells still need energy to survive, and they switch to a back-up mechanism to obtain energy. Fat cells begin to break down, producing compounds called ketones. Ketones provide some energy to cells but also make the blood too acidic (ketoacidosis). Since plasma glucose diabetic ketoacidosis exceed the renal threshold; glucose is always present in the urine of patients (glycosuria) with ketoacidosis, the pH of the blood is important in determining the severity of the condition. Blood normally has a pH of 7.35-7.45, maintained by the buffering systems, the most important of which is the bicarbonate buffer system. When acids accumulate in the blood, they dissociate with an increase in hydrogen ion concentration. Bicarbonate can usually neutralise hydrogen ions by incorporating them into water. DKA is associated with electrolyte imbalances; sodium and potassium levels in particular are affected. Serum sodium levels may be low, high or normal. When evaluating the serum sodium level, it is helpful to remember that hyperglycemia causes a shift of free water into the extracellular space, diluting the measured sodium concentration which results in lost of sodium via lie urine as a result of osmotic diuresis. In addition, vomiting, a common feature of ketoacidosis is associated with a loss of sodium from the gastrointestinal tract. This might not always be reflected in the blood results because it is a measure of concentration and, as has already been illustrated, dehydration will be present. Normal plasma sodium levels are maintained between 135 and 145mmol/l, however, despite the actual deficit, patients with DKA might display wide-ranging plasma sodium levels depending on the relative losses of water and sodium. Total body potassium is always depleted in ketoacidosis as potassium is also lost in urine and vomit. The plasma concentration of potassium, however, remains relatively high due to the passage of potassium out of the cells and into the extracellular fluid. One of the mechanisms that normally control the passage of potassium into and out of cells is the sodium/potassium pump. This pump requires intracellular glucose, which is not available in ketoacidosis, consequently, the pump cannot function and potassium leaks out of the cell and into the plasma. Furthermore, potassium is freely exchangeable with hydrogen across the cell membrane. If the hydrogen concentration is high as in DKA, hydrogen will move into the cell in exchange for potassium. So, despite an overall potassium deficit, plasma levels are usually raised in ketoacidosis, at the expense of the body cells. The kidneys can malfunction, resulting in kidney failure that may require dialysis or kidney transplantation. Doctors usu ally check the urine of people with diabetes for abnormally high levels of protein (albumin), which is an early sign of kidney damage. At the earliest sign of kidney complications, the person is often given angiotensin-converting enzyme (ACE) inhibitors, drugs that slow the progression of kidney disease by decreasing blood flow to the kidneys which prevent the kidneys from excreting normal amounts of potassium leads to mild hyperkalaemia. The result obtained for patient-4 corresponding with the clinical findings found in diabetic ketoacidosis. The sodium is reduced (130 mmol/L) and the potassium reading is relatively high (5.8 mmol/L) when compared with the normal reference range. There is a marked increase in urea (15.6 mmol/L) because as mentioned earlier the kidneys can malfunction, resulting in kidney failure that will concentrate fluid in the extracellular compartment. Conclusion Patient 1 is suffering from Addisons disease Patient 2 is suffering from Coons syndrome Patient 3 is suffering from chronic renal failure Patient 4 is suffering from diabetic ketoacidos Questions Calculate the osmolarity (mmol/L) for each patient. Why would patients3s (the diabetic) osmolarity be underestimate? Osmolarity is a property of particles of solute per liter of solution. If a substance can dissociate in solution, it may contribute more than one equivalent to the osmolarity of the solution. The expected osmolarity of plasma can be calculated according to the following formula. Calculated osmolarity (mOsm/kg) = 2*[Na +] + 2*[K+] + (glucose) + (urea) Patient 1 = 2 x 116 + 2 x 6.2 + [glucose] + 9.7 Patient 2 = 2 x 144 + 2 x 2.8 + [glucose] + 6.3 Patient 3 = 2 x 137 + 2 x 8.7 + [glucose] + 78.9 Patient 4 = 2 x 130 + 2 x 5.8 + [glucose] + 15.7 The final result is not obtained as the glucose values are not given, so the calculation can not be done without glucose values. The patient 3 (the diabetic) osmolarity is underestimated because of insulin deficiency, the cells uptake of glucose, which causes hyperglycaemia. What is the abnormality in the clinical condition Diabetes Insipidus, and how does it affect water electrolyte balance? Many different hormones help to control metabolic activities within the body. One of these is called anti-diuretic hormone (ADH) and its function is to help control the balance of water in the body. It does this by regulating the production of urine. ADH is produced by the hypothalamus and then stored in the pituitary gland until it is needed. Diabetes Insipidus usually results from the decreased production of antidiuretic hormone. Alternatively, the disorder may be caused by failure of the pituitary gland to release Antidiuretic hormone into the bloodstream. Other causes of diabetes Insipidus include damage done during surgery on the hypothalamus or pituitary gland; a brain injury, particularly a fracture of the base of the skull; a tumor; sarcoidosis or tuberculosis; an aneurysm (a bulge in the wall of an artery) or blockage in the arteries leading to the brain; some forms of encephalitis or meningitis; and the rare disease Langerhans cell granulomatosis (histiocytosis X). Another type of diabetes Insipidus, nephrogenic diabetes Insipidus, may be caused by abnormalities in the kidneys. Diabetes Insipidus suspected in people who produce large amounts of urine. They first test the urine for sugar to rule out diabetes mellitus. Blood tests show abnormal levels of many electrolytes, including a high level of sodium. The best test is a water deprivation test, in which urine production, blood electrolyte (sodium) levels, and weight are measured regularly for a period of about 12 hours, during which the person is not allowed to drink. A doctor monitors the persons condition throughout the course of the test. At the end of the 12 hours, or sooner if the persons blood pressure falls or heart rate increases or if he loses more than 5% of his body weight, the doctor stops the test and injects Antidiuretic hormone. The diagnosis of central diabetes Insipidus is confirmed if, in response to Antidiuretic hormone, the persons excessive urination stops, the urine becomes mor e concentrated, the blood pressure rises, and the heart beats more normally. The diagnosis of nephrogenic diabetes Insipidus is made if, after the injection, the excessive urination continues, the urine remains dilute, and blood pressure and heart rate do not change. How do diuretics work? And what are the three main groups of diuretics? Diuretics work in the kidneys to increase the elimination of water and electrolytes, thereby causing more urine to form. Because the amount of fluid in the body is lowered, blood pressure goes down, too. Different chemical types work in different areas of the nephrons; so many different classes of diuretics are used. Three of the most common classes of diuretics are: Thiazide and Thiazide-Like Diuretics Drugs containing the chemical Thiazide and similar chemicals like indapamide and metolazone are suggested as the first drugs to try for most people with high blood pressure. They affect the distal convoluted tubule, where large amounts of sodium and water are absorbed back into the body. By blocking the re-absorption process, these drugs force more sodium and more water into the urine to be removed from the body. Thiazides may also relax the muscles in blood vessel walls, making blood flow more easily. Loop Diuretics More powerful than the Thiazide are classes of diuretics that work in the area of the Loop of Henle. These loop diuretics mainly interfere with the bodys re-absorption of chloride, but they also keep sodium from re-entering the blood. Unfortunately, loop diuretics are also more likely to promote the elimination of calcium, magnesium and especially potassium. Shortages of any of these essential electrolytes can cause serious problems such as irregular heartbeats. Potassium-Sparing Diuretics The third common group of diuretics consists of drugs that are much weaker than the Thiazides or the loop diuretics but potassium-sparing diuretics do not reduce potassium levels nearly as much as other kinds of diuretics do. They inhibit aldosterone and/or block sodium reabsorption and inhibit potassium excretion in the distal tubule.