Regenerative Medicine Course - Essay Example

? Regenerative Medicine Regenerative Medicine Question a) Define systeolic heart failure Systolic heart failure can be defined as the inability of the heart to supply the metabolic requirements of the body tissues. In this form of heart failure, myocardial shortening is significantly impaired leading to a shift of the length-tension relationship to the right of the normal pressure-volume relationship (Mulholland and Doherty, 496). B) Describe the impact of neurohormonal activation on the progression of left ventricular dysfunction The most important pathways in the neurohormonal activation in the pathogenesis and progression of heart failure include the renin-angiotensin-aldosterone and the sympathetic nervous system. Some of the adverse effects of neurohormonal activation include fluid retention, vascular dysfunction and cardiac remodeling. The system is important in maintaining organ perfusion but sometimes maladaptive activation leads to deterioration in the left ventricular function (Greenberg, Bernard, Narayan and Teerlink 354). Studies have shown that inhibiting of the mentioned key functional areas of the neurohormonal activation system including RAAS and SNS activation leads to significant reduction in morbidity and mortality in a broad spectrum of heart failure patients. c. Give an example of a class of medications that counteracts the effects of neurohormonal activation and describe its mechanism of action. Some of mediations that counteract the effects of neurohormonal activation include beta-blockers which work by inhibiting beta-adrenergic receptor activation by catecholamines resulting in reversing or inhibiting left ventricular remodeling, anti-arrhythmic effects and improvement of myocardial diastolic perfusion. This form of medication also results in reduction in myocardial oxygen consumption as well as reduction in production of pro-inflammatory cytokines. This class of drugs leads to improvement of ventricular performance and form the basis for heart failure therapy. However, beta-blockers fall under homogenous class of drugs with different efficacy levels. Question 2 If you were a physician seeing a patient with type 1 diabetes mellitus. How would you advise them about the role of transplantation and the advantages/disadvantages of islet vs. pancreas transplantation? Pancreas transplantation has been proven to have positive effect on the quality of life among diabetic patients and restoration of physical activity. Another advantage of pancreas transplantation is that it prevents recurrence of diabetic nephropathy. Pancreas transplantation has been associated with numerous risks including substantial risk for cardiovascular disease. Pancreas transplantation patients are also exposed immunosuppression related risk of opportunistic infection, cancer and cardiovascular disease. The process of pancreas transplantation is also associated with increase morbidity and mortality risks compared to other forms of diabetes I treatment. In some patients, complications of diabetes results in such poor quality of life with the disadvantages cancelling the various benefits of pancreas transplantation (Eisenbath 136). Therefore, assessment of the suitability of pancreas transplantation must balance the realistic expectations of benefits from pancreas transplantation and the expected disadvantages. The most important benefit associated with successful pancreas transplantation revolves around prevention of nephropathy recurrence evident in kidney transplantation as treatment to diabetes. Islet cells transplantation has many benefits including the ability to deliver pancreatic islets through a percutaneous catheter into the portal vein under local anesthesia. In addition, pretreatment of the islet cells with immunosuppressive agents can reduce their immunogenicity. Islet transplantation offer significant advantages associated with the potential for modifying tissue immunogenicity through in vitro culture and gene therapy (Eisenbath 137). It also allows for the use of alternative tissue sources through the islet graft technique. However, the disadvantages of this transplantation include acute to chronic rejection, lack of an adequate number of islets per transplant and difficulty with isolation and preservation of islet cells. Based on the comparison between the two forms of transplantation, I would recommend islet transplantation because it has limited risks associated with immunosupression agents and less organ resistance compared to pancreas. Question 3 List three (3) major acute or chronic complications of decompensated cirrhosis with two (2) principles of management and the rationale for each. Decompensated cirrhosis manifests itself through several symptoms including variceal hemorrhage, encephalopathy, ascites and jaundice. Ascites forms one of the major chronic complication associated with sodium retention and sinusoidal hepertension. The pathogenesis of ascites in cirrhosis mainly reflects increased intrahepatic resistance due to fibrosis, which raises portal pressures (Sidebotham and Levy 348). Compensatory mechanisms cause splanchnic vasodilation, resulting in a decrease in effective arterial blood volume. The imbalance of elevated hydrostatic pressure due to portal hypertension and decreased oncotic pressure play a critical role in the development of ascites . In this case, sodium retention is key to the development of ascites. The mainstay of management of ascites involves sodium restriction and judicious diuresis. Patients diagnosed with the complication are advised to stay on a sodium-restricted diet of 2g/day. Another chronic complication associated with decompensated cirrhosis include variceal hemorrhage which is occurs as a result of portal hypertension or hepatic insufficiency. Gastroesophageal varices may also result because of portal hypertension although the development of variceal growth and hemorrhage may be attributed to hyperdynamic circulation (Sidebotham and Levy 348). Acute variceal hemorrhage can be controlled through endoscopic therapy administered either as variceal band ligation or sclerotherapy. However, pharmacological therapy involving octreotide, somatostatin and terlipressin have found to have almost equal efficacy the endoscopic therapy. The other chronic complication is known as hepatorenal syndrome associated with extreme vasodilatation accompanied by an extreme decrease in effective blood volume. This complication also results into renal vasocontriction and renal failure. Liver transplantation emerges as the most effective way of managing this complication although vasoconstrictors combined with albumin can help in reversing the condition. Question 4 Describe the main indications for the use of extracorporeal life support therapies (ECLS) for lung failure and discuss the possible configurations of ECLS. Extracorporeal life support (ECLS) intervention involve the use a n artificial heart (Pump) and lung (membrane oxygenator) to replace organ function for days or weeks, to allow for the diagnosis, treatment, and organ recovery or replacement (Cypel and Keshavjee 245). The primary circumstance for use of ECLS in patients with severe respiratory failure include experiences of optimal ventilator and medical management and with the risk of dying from ARDs greater than 80%, transpulmonary shunt fraction of greater than 30% despite maximal conventional therapy. The ECLS intervention is characterized by several indications including acute, severe heart or lung failure not improving under conventional management. The major risk of this procedure involves bleeding in which health care providers must ensure continuous bedside attendance of a specialist whose primary role is to measure the ACT and platelet counts at every frequent interval and titrate heparin dose and platelet infusions accordingly. Properly managed, ECLS can be used for weeks without hemolysis, devise failuire, clotting or bleeding. However, several complications have been reported during execution of ECLS including severe hemorrhage, cannulation site, neurological and renal failure. In order to prevent other complications in the process, referral to an ECLS center should be done early enough if a patient is suspected to have the need for the technology (Cypel and Keshavjee 245). Question 5 Although dialysis is the only form of chronic ambulatory replacement therapy, the present outcome of a patient with end stage renal disease is suboptimal. Identify your strategy to improve the present clinical practice to enhance patient’s quality or quantity of life. Suboptimal dialysis in patients with end stage renal disease could be attributed to several factors including poor adherence to medication as well as poor perception of oral therapy (Neri et al.). In this case, the key strategy in ensuring improved quality of life and clinical outcomes would include establishment of ways to promote adherence to medications and change of perception about the condition and some of the interventions. Reported poor adherence to medication which contributes significantly to the suboptimal dialysis has been attributed to the high number of drugs or tablet counts prescribed for use by the patients. Effort should be put in reducing the burden associated with such medications through recommendation of stronger drugs with fewer tablet counts to motivate patients to adhere to the medication. This step will be crucial in ensuring that patients develop a positive attitude towards adherence to the prescribed medications prior to the dialysis process. Modulation of the regime complexity can play an important role in enhancing medication adherence with consequent improvement in the patients’ outcomes. Moreover, the Life Options Rehabilitation Advisory Council (LORAC) has identified five core principles, known as the “5 E’s”- Encouragement, Education, Exercise, Employment and Evaluation (Auer 77). This provides guidelines for enhancing patients’ quality of life with emphasize on the importance of implementing each principle to get better outcome in ESRD patients. Patients on dialysis focus less on the clinical procedures and more on the activities during the procedures such as eating, reading and dozing. Dialysis done at home plays an important role in improving compliance and reducing the burden of patients commuting to hospitals. Dietitian play an important role in medical nutrition therapy by providing easy to follow-diet instructions, and encouragement of patients participate in special cooking classes designed for patients with renal disease (Chau et al.) Provision of counseling and identifying community services/recourse to patients and families help cope with the disease as well as provide encouragement that generates positive impact on their adjustment. Nevertheless, this can only be achieved with proper education and counseling of patients and family members on the importance of adhering to the medication as way of nurturing appropriate or positive attitude towards the dialysis intervention as well as the health condition being treated. Therefore, modulation of regime or reduction of drug burden among the end stage renal disease and attitude change are the main strategies that can enhance the quality of life for patient as well patient outcomes. Question 6 Transplantation for end stage organ failure is currently limited by donor organ availability. Discuss the current barriers to organ donation and potential strategies to increase the number of organs available for transplantation. One of the barriers to organ donation lies in people’s perception and lack of knowledge or information about the importance and risks associated with process. The growing demand for such organ amidst the limited number of organ donors has seen a rise in demand for living donations which are significantly limited by the great risks involved in practice (Cameron and Forsythe 69). Death risks for some organs such as the liver among the donors has particularly limited the number of donors as there are very few people willing to take such risks. Other barriers to organ donation revolve around the lack of proper legislature to regulate the practice in most countries. In addition, ethical issues surrounding the practice further pose significant challenges as people continue to question the ethical standing of the practice. However, organ donation can be enhanced through establishment of proper mechanisms ranging from legal, ethical, involvement of the National Health Service, co-ordination of the entire process and creation of reliable organ retrieval arrangements. In addition, the entire medical fraternity requires proper training to handle issues of organ donation as well as creation of awareness among the public, proper promotion of the practice and perhaps provision of incentives through the National Health Service (Cameron and Forsythe 74). Question 7 Based on the different mechanisms of respiratory failure, please explain for each one of them the physiopathology of the alteration of the normal exchange of O2 and CO2. Some lung disorders result in severe acute respiratory failure in previously healthy subjects; a condition often characterized the acute respiratory distress syndrome characterized by severe hypoxemia refractory to high concentration of inspired oxygen (Sidebotham and Levy 397). The mechanism leading to intrapulmonary shunt includes gas absorption caused by complete distal airways occlusion, a reduction in ventilation to units with inspired ratios below a critical level. This particularly explains the changes in oxygen and carbon dioxide due to absent or deficient surfactant, and lung tissues. Respiratory distress leading respiratory failure occurs due to either hypoxemia which is a potent respiratory stimulant or increased work of breathing caused by reduced respiratory compliance, increased airways resistance, or the need for increased minute ventilation secondary to increased oxygen consumption or carbon dioxide production. Respiratory failure may also be attributed to pulmonary disease which leads to reduced lung capacity, increased airways resistance and potential obstruction of the lungs. Cardiac failure also indirectly leads to respiratory failure in which the effects of reduced cardiac output on mixed venous oxygen saturation. These changes account for the changes in oxygen levels during this condition. The other mechanism involve the central nervous system and neuromuscular dysfunction which lead to the oxygen and carbon dioxide changes through hypoventilation, loss of protective airway reflects, and impaired swallowing. Hypoventilation causes hypercarbia, and severe, hypoxemia contributes significantly to the oxygen and carbon dioxide changes associated with the respiratory failure condition (Sidebotham and Levy 398) . All these mechanisms for respiratory failure provide clear leads on the sources of the oxygen and carbon dioxide changes associated with the condition. Work Cited Auer, J. Psychological perspectives. In Renal Nursing (N. Thomas, ed) 2nd edn. Bailliere Tindall, Philadelphia, 2002. Print. Cameron and Forsythe. “How can we improve organ donation rates? Research into the identification of factors which may influence the variation. NEFROLOGIA 21 (2001): 68-77. Chau et al. "Rehabilitation of Patients with End-stage Renal Disease”, Renal unit, Department of Medicine, Queen Elizabeth Hospital. Medical Section, 8.2 (2003). Cypel, Marcelo and Shaf Keshavjee. “Extracorporeal life support as a bridge to Lung transplantation. Clinical Chest Medicine 32 (2011), 245-251. Eisenbath, George. Type 1 Diabetes: Molecular, Cellular and Clinical Immunology. London: Springer, 2004. Print. Greenberg, Barry, Denise, Bernard, Sanjiv, Narayan and John, Teerlink. Management of Heart Failure. Hoboken, NJ: John Wiley & Sons, 2011. Print. Mulholland, Michael and Gerard, Doherty. Complications in Surgery. New York, NY: Lippincott Williams & Wilkins, 2011. Print. Neri et al. “ Regimen complexity and prescription adherence in dialysis patients. American Journal of Nephrol, 34 (2011): 71-76. Sidebotham, David and Jerrold, Levy. Cardiothoracic Critical Care. London: Elsevier Health Sciences, 2007. Print. Read More