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Cold-blooded animals such as frogs discount 10 mg prozac with visa, snakes and lizards do not need lung surfactants for breathing purchase prozac. As a result they require about a factor of ten less oxygen than warm- blooded animals of comparable size trusted prozac 10 mg. Therefore, cold-blooded animals can function with correspondingly smaller lung surface area. The alveolal radii of these animals are ten times larger than those of warm-blooded animals (see Exercise 9-9). An alveolus of larger radius requires correspondingly lower pressure to overcome surface tension eliminating the need for lung surfactants. However, the cornea, which is the transparent surface layer of the eye, does not contain blood vessels (this allows it to be transparent). The cells in the cornea receive oxygen by diusion from the surface layer of tear uid, which contains oxygen. This fact allows us to understand why most contact lenses should not be worn during sleep. Of course, when people sleep they do not blink; therefore, the corneas under their contact lenses are deprived of oxygen. Fish using air bladders to control their buoyancy are less stable than those using porous bones. A scuba diver breathes air from a tank which has a pressure regulator that automatically adjusts the pressure of the inhaled air to the ambient pressure. If a diver 40 m below the surface of a deep lake lls his lungs to the full capacity of 6 liters and then rises quickly to the surface, to what volume will his lungs expand? Assume that the average velocity of the molecules is 104 cm/sec and that the mean free path is 108 cm. Show that if the oxygen requirement of an animal is reduced by a factor of 10, then within the same lung volume, alveolar radius can be increased by a factor of 10. After many decades of experience with heat phenomena, scientists formulated two fundamental laws as the foundation of thermodynamics. Perhaps the simplest state- ment of the Second Law of Thermodynamics is that spontaneous change in nature occurs from a state of order to a state of disorder. In 1840 Mayer was the physician on the schooner Java, which sailed for the East Indies. While aboard ship, he was reading a treatise by the French scientist Laurent Lavoisier in which Lavoisier suggested that the heat produced by animals is due to the slow combustion of food in their bodies. Lavoisier further noted that less food is burned by the body in a hot environment than in a cold one. He noticed that the venous blood, which is normally dark red, was nearly as red as arterial blood. Because in the tropics less fuel is burned in the body, the oxygen content of the venal blood is high, giving it the brighter color. Mayer then went beyond Lavoisiers theory and suggested that in the body there is an exact balance of energy (which he called force). The energy released by the food is balanced by the lost body heat and the work done by the body. Mayer wrote in an article published in 1842, Once in existence, force [energy] cannot be annihilated it can only change its form. Conservation of energy is implicit in all our calculations of energy balance in living systems. The body of an animal contains internal thermal energy Et, which is the product of the mass and specic heat, and chemical energy Ec stored in the tissue of the body. Without going into detailed calculations, the rst law allows us to draw some conclusions about the energetics of the animal. For example, if the internal temperature and the weight of the animal are to remain constant (i. An imbalance between intake and output energy implies a change in the sum Ec + Et. The First Law of Thermodynamics does not forbid the reverse process, whereby the heat from the oor would enter the object and be converted into kinetic energy, causing the object to jump back on the table. The irreversibility of these types of events is intimately connected with the probabilistic behavior of systems comprised of a large ensemble of subunits. Suppose that we now shake the tray so that each coin has an equal chance of landing on the tray with either head or tail up. Of these, only one yields the original ordered arrangement of three heads (H,H,H). Because the probabilities of obtaining any one of the coin arrangements in Table 10. As the number of coins in the experiment is increased, the probability of returning to the ordered arrangement of all heads decreases. With 10 coins on the tray, the probability of obtaining all heads after shaking the tray is 0. We could shake the tray for many years without seeing the ordered arrangement again. As the number of coins in the ensemble increases, the probability of returning to an ordered arrangement decreases. In other words, if we disturb an ordered arrangement, it is likely to become disordered. This type of behavior is characteristic of all events that involve a collective behavior of many components. The Second Law of Thermodynamics is a statement about the type of prob- abilistic behavior illustrated by our coin experiment. One statement of the second law is: The direction of spontaneous change in a system is from an arrangement of lesser probability to an arrangement of greater probability; that is, from order to disorder. This statement may seem to be so obvious as to be trivial, but, once the universal applicability of the second law is recognized, its implications are seen to be enormous. We can deduce from the second law the limitations on information transmission, the meaning of time sequence, and even the fate of the universe. One important implication of the second law is the limitation on the con- version of heat and internal energy to work. This restriction can be understood by examining the dierence between heat and other forms of energy. In many cases, energy is being transferred to or from a body by dierent methods, and keeping track of each of these is often not possible and usually not necessary. The main feature that distinguishes heat from other forms of energy is the random nature of its manifestations. Similarly, when heat is transferred by radiation, the propagating waves travel in random directions.
The most thorough information is available for a Particularly favourable results have been described for the com- combination therapy with metformin and sulphonylureas (Her- bination of insulin and metformin (Yki-Jrvinen et al prozac 20mg on-line. Evaluations of the safety of combination tite and fullness purchase prozac 10 mg on-line, diarrhoea is relatively rare prozac 10 mg without a prescription. The most dangerous therapy with metformin and sulphonylureas have led to dier- side eect is lactic acidosis, which is extremely uncommon. The risk of the fact that the patients who were treated with a sulphonylurea death is about a third of this gure. Renal insuciency and cardiac combination therapy in a Scandinavian study (Olsson et al. In a recent Cochrane analysis of patient group receiving combination therapy in this study con- 206 prospective comparative studies spanning 47846 patient sisted of a cohort with a longer diabetes duration and was less years with metformin and 38221 patient years without met- well controlled (Olsson et al. In a 5-year Canadian formin, no evidence of an increased risk of lactic acidosis related observational study of 12272 patients who had recently begun to metformin was found (Salpeter et al. Likewise in an 8-year Scottish observational study Pancreatitis of 5730 patients who had recently begun treatment with oral Alcoholism antidiabetic drugs (Evans et al. Medical Antihyperglycaemic Treatment of Diabetes Exp Clin Endocrinol Diabetes 2009; 117: 522557 526 Guidelines 1. Acarbose can be com- enclamide that was used frequently then is now associated with bined with any therapeutic principle that lowers blood glucose, possibly unfavourable mortality data. Exactly 50 years after its and also contributes to further signicant reduction of HbA1c introduction, metformin is undergoing a renaissance of a kind (Chiasson et al. It has not tralian retrospective observational study, metformin was yet been established beyond doubt whether this actually pre- observed to produce at least equally good results for patients of vents the patient from developing diabetes mellitus, or whether normal weight as for overweight patients in terms of diabetes it is simply slowed. Today, metformin is used in combination with all other available antidiabetic medications 1. The favourable view of metformin is also sup- once daily, whereby the most suitable meal for taking the pre- ported by a new Cochrane analysis (Saenz et al. Increasing the dosage to a total daily dose of more than the oligosaccharides consumed with food remains in the intes- 100200mg does not appear to bring any benets (recommen- tines. Currently, only acarbose and migli- Similar titration is also advisable for miglitol. Therefore, voglibose is not there does appear to be a linear dose-eectiveness relationship mentioned in this guideline. Medical Antihyperglycaemic Treatment of Diabetes Exp Clin Endocrinol Diabetes 2009; 117: 522557 Guidelines 527 1. For every tropic medications or insulin, hypoglycaemia can only be treated one percent elevation of the baseline-HbA1c, the estimated orally or with glucose and not with oligosaccharides. Contraindications also exist for patients with adhere to the treatment regimen (Holman et al. Because of their pharmacologically dif- does not improve beta-cell function (Chang et al. An eect on surrogate parameters has been on serum lipids has not been conrmed (van de Laar et al. Postprandial reduction of D-dimer and pro- near- normoglycaemic blood glucose levels. Severe side eects thrombin fragments, and therewith also a possible reduction in occur rarely, but gastrointestinal side eects are frequent, and the degree of activation of haemostasis was observed in type 2 they tend to discourage patients from adhering to the treatment diabetics receiving acarbose (Ceriello et al. Medical Antihyperglycaemic Treatment of Diabetes Exp Clin Endocrinol Diabetes 2009; 117: 522557 528 Guidelines 1. Rosiglitazone can be Rosiglitazone and pioglitazone are selective agonists of the taken with or without food. For These substances improve blood glucose control by reducing patients with mild to moderate renal insuciency (creatinine insulin resistance in adipose tissue, skeletal muscle and liver clearance > 30 ml / min), the dosage does not need to be ( Balfour et al. No informa- pioglitazone) tion is available with regard to dialysis patients, so these patients a) With metformin: for patients whose blood sugar is not su- must not receive pioglitazone (Technical information on Actos, ciently controlled despite oral monotherapy with the maximum August 2007). This dose There is a comparison of the sustained therapeutic eect of ini- can be increased to 8mg/daily after 8 weeks if necessary. Ros- tial monotherapies for diabetes mellitus type 2 with rosiglita- iglitazone can be administered in one or two doses per day, zone, metformin and glyburide (Kahn et al. After ve years, therapy failure dened as fasting blood with two administrations per day than with one, without result- sugar > 180 mg / dl was observed in 15% of patients treated ing in a signicant dierence. In combination with a sulphonylu- with rosiglitazone, 21% of patients treated with metformin, and rea, care should be taken when increasing the dosage to 8mg/d. The dierences were sig- It should be preceded by an appropriate medical examination to nicant. This last nding was conrmed was treated with pioglitazone, the fraction of patients who had to in a further meta-analysis (Lago et al. The same authority recom- studies with rosiglitazone as the study medication, which mends that rosiglitazone not be used for patients with ischaemic detected a signicant increase in the risk of myocardial infarc- coronary disease and/or peripheral arterial occlusive disease (press tion (Odds ratio 1. These points compared with control groups (placebo and comparison sub- have also been incorporated into the current Technical Information stances). Medical Antihyperglycaemic Treatment of Diabetes Exp Clin Endocrinol Diabetes 2009; 117: 522557 530 Guidelines ( Bailey et al. Medical Antihyperglycaemic Treatment of Diabetes Exp Clin Endocrinol Diabetes 2009; 117: 522557 Guidelines 531 Advantages Disadvantages therapy (Rosenstock et al. This pressure ) -cytotropic eect occurs in hyper-, normo- and hypoglycaemia improvement of micro- depending on dosage. In chemical terms, repaglinide and nateg- linide are not sulphonylureas, but their molecular structures are 1. Medical Antihyperglycaemic Treatment of Diabetes Exp Clin Endocrinol Diabetes 2009; 117: 522557 532 Guidelines contraindication for metformin exists. However, there is no clear proof that therapy with glibenclamide (in addition to diet treatment) 1. The benet-risk ratio of combination often with glimepiride therapy than with glibenclamide therapy therapy of a sulphonylurea with metformin has not been estab- (Holstein et al. The of the sulphonylureas available in Germany should be started assumption that sulphonylureas increase the risk of cardiovas- gradually at the following daily doses: 1. A number of gliclazide, 6mg glimepiride, 120mg gliquidone, or 2g tolbuta- other studies yielded indications of unfavourable eects by glib- mide) and recommendations to take the entire daily dose at enclamide on the heart (e. But glibenclamide should also be with previously compromised cardiac conditions, and when taken only once a day (up to 7mg in the morning), because there sulphonylureas were combined with metformin (Olsson et al. However, the retrospec- dosage of glibenclamide several times in the day, and because tive design of all of these studies makes it impossible to rule out taking another 3. On the pensation for metabolic acidosis, precoma or coma other hand, macrovascular complications and diabetes-related Pancreatectomy death were only lowered with metformin, not with sulphonylu- Impaired renal function (treatment with gliquidone possible reas.
Investigations Many systemic diseases may cause the clinical features r Chest X-ray shows cardiac enlargement with signs of of dilated cardiomyopathy buy cheap prozac 20mg line, e buy 20mg prozac. Left ventricu- lar failure causes an elevated end-diastolic pressure with coronary artery disease buy discount prozac 20mg on line, as this may present similarly resultant increase in pressure within the pulmonary cir- without any history of angina or myocardial infarct. Clinical features r Management Symptoms are dependent upon the degree of cardiac r General measures include bed rest, uid restriction failure. Tachycardia boembolicdiseaseorapresenceofintracardiacthrom- is common and low perfusion results in peripheral bous should be anti-coagulated. Severe cases may vascular shutdown (small thready pulse, cold extrem- benet from anti-coagulation without other risk fac- itiesandperipheralcyanosis). Ankle Prognosis and/or sacral oedema, mild hepatomegaly and jaun- Theprognosisisverypoor. Youngpatientsmaybetreated dice, due to hepatic congestion or tricuspid regurgita- with cardiac transplantation. Hypertrophic cardiomyopathy Macroscopy/microscopy The ventricles are dilated (left more than right), the Denition chamber walls are thin and the muscle poorly contrac- Hypertrophicorhypertrophicobstructivecardiomyopa- tile. Complications Aetiology Atrial brillation is common, particularly in alcoholic r Half the cases are due to an autosomal dominant in- cardiomyopathy, and bouts of ventricular tachycardia herited point mutation of the myosin heavy chain, may occur. Mural thrombosis may occur in either ven- which codes for a component of the cardiac muscle tricle with the associated risk of systemic embolisation. This may raphy cannot obtain adequate views particularly in result in obstruction to the outow of the left ventricle, apical hypertrophy. Clinical features Hypertrophic cardiomyopathy often presents similarly Management r -blockade is the mainstay of treatment as this lowers to aortic stenosis with dyspnoea, angina, syncope, or sudden death. Initially the pulse is jerky with a rapid outow due to hypertrophy, in the late stages ob- prevent ventricular arrhythmias and there is increas- struction results in a slow rising pulse. This may pertrophied septal wall (myotomy/myectomy) is in- be varied by dynamic maneouvres or drugs that can al- dicated with, where necessary, a mitral valve replace- ter the degree of functional obstruction. Surgical intervention is usually reserved for sound is often heard caused by ventricular lling due to severely symptomatic patients. ItisassociatedwithWolff diuretics should only be used with care as these in- ParkinsonWhite Syndrome. Prognosis Macroscopy/microscopy Factors suggesting a worse prognosis include young age Hypertrophy is asymmetrically distributed. Disorganised branching of abnormal, short, thick muscle bres, in which there are large nuclei. Pathophysiology Inltrativediseasecausingadecreaseinventricularcom- Incidence pliance (increase in stiffness) affecting the myocardium. The result is a failure of relaxation during diastole, im- pairment of ventricular lling and compromise of car- Aetiology diacoutput. Valvesmayalsobeaffectedbytheunderlying Although infective endocarditis may occur on normal disease. Enlarged liver, ascites and peripheral The clinical pattern is dependent on the infective organ- oedema may all be seen. It is an upper Thrombus formation is common, and arrhythmias and respiratory tract commensal. Differentiation from r There are many other rarer bacterial causes and fungal constrictive pericarditis using these methods can be dif- causes include Candida, Aspergillus and Histoplasma. Denitive diagnosis may require cardiac catheter- The disease is also dependent on the portal of entry, and isation and cardiac biopsy. Low-dose diuretics and vasodila- r Central lines and intravenous drug abuse (tricuspid tors may provide some relief from symptoms. Pathophysiology Prognosis The clinical picture of infective endocarditis is a balance The condition is commonly progressive. The result is either an r Splinter haemorrhages, linear dark streaks seen in the acute infection or a more insidious (subacute) course. The disease process predisposes to the forma- mucosa of pharynx and retinal haemorrhages may tion of thrombus with the potential for emboli. Cytokine be seen (Roths spots are haemorrhages with a pale generation causes fever. Afever and a new or changing murmur is endocardi- r Full blood count shows an anaemia with neutrophilia. Urine cultures may be required to identify r Acute bacterial endocarditis presents with fever, new aurinary tract infection, and renal ultrasound may be or changed heart murmurs, vasculitis and infective indicated to demonstrate a renal abscess. Severe acute heart failure may occur due to r Chest X-ray may show heart failure or pulmonary in- chordal rupture or acute valve destruction. General signs: r Malaise, pyrexia, anaemia and splenomegaly, which Complications may be tender. Cerebral emboli may cause infarction or my- disturbance due to the valve lesion(s), e. Once cultures are sent, intravenous antibiotics should be commenced based on the most likely pathogens if there is a high suspicion of Hypertension and vascular bacterial endocarditis. The r When the culture results are known endocarditis World Health Organisation latest guidelines dene hy- should be treated with the most appropriate antibi- pertension with three grades of severity that reect the otics. It is best to have a multidisciplinary approach fact that systolic and diastolic hypertension are indepen- with early microbiological and surgical advice. M > F The timing of surgery is a balance between the desire to eradicatebacteriapriortotheprocedureandtheneedfor early surgery due to the compromised haemodynamic Geography state. Aftersurgeryafullcourseofdrugtreatmentshould Rising prevalence of hypertension in the developing be given to eradicate the organisms. Prognosis r Modiable: Obesity, alcohol intake, diet (especially Despite advances in treatment, overall mortality is still high salt intake). Complications Hypertension is a major risk factor for cerebrovascular Pathophysiology disease (strokes), heart disease (coronary artery disease, r Hypertension accelerates the age-related process of left ventricular hypertrophy and heart failure) (see Table arteriosclerosis hardening of the arteries and predis- 2. Arterioscler- include peripheral vascular disease and dissecting aortic osis, through smooth muscle hypertrophy and intimal aneurysms. In r The chronic increased pressure load on the heart re- severehypertension,retinalhaemorrhages,exudatesand sults in left ventricular hypertrophy and over time this papilloedema are features of malignant hypertension. Saltand r Benign hypertension and small arteries: There is hy- water retention occurs, which can itself worsen hyper- pertrophy of the muscular media, thickening of the tension. In cases of doubt, r Routine investigations must include fasting plasma 24-hour blood pressure recordings may be helpful such glucose, serum total cholesterol and lipid prole, as when white coat hypertension is suspected. Management Peripheral arterial disease Treatment is based on the total level of cardiovascular Denition risk and the level of systolic and diastolic blood pressure Peripheralarterialdiseasedescribesaspectrumofpatho- (see Tables 2. Stopping smoking as well as the ac- tions mentioned above will also reduce overall cardio- Age vascular risk. If after 3 months their M > F systolic blood pressure is above 139 or the diastolic above 89, treatment should be started. The remainder Geography of patients and those with low or average risk should More common in the Western world. Atheromatous plaques form especially in larger vessels at areas of haemodynamic stress such as at the bifurcation Prognosis of vessels and origins of branches.
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