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BIOL122 Human Biological Science

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BIOL122 Human Biological Science

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Course Code: BIOL122
University: Australian Catholic University

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Country: Australia

Questions:
Question 1.
 
Two major pathological changes that occur in the respiratory tract during an asthma attack are:
• Bronchial smooth muscle contraction• Increased mucus production
 
Explain how these pathological changes arise in your person/client (ie. the pathophysiology).
 
Question 2.
 
The clinical manifestations of asthma include:GROUP A GROUP BCough Airway oedemaHypoxia Increased respiratory rateWheeze Increased heart rateTight chest Dyspnoea
 
Choose ONE clinical manifestion from GROUP A and ONE clinical manifestation from GROUP B and relate them to the underlying pathophysiology for your person.
 
Question 3.The following drugs are used in the management of asthma.• Salbutamol• Inhaled corticosteroid
 
Choose ONE that is appropriate for your person/client. Discuss why it can be used by your person/client by referring to its mechanism of action.
 
Question 4. Answer both parts (a) and (b)(a) The drug chosen in question 3 acts topically and systemically. Explain why.(b) Describe the educational advice you would give your person/client with respect to the administration of the drug chosen in question 
Answer:
Introduction
Diabetes mellitus is  known as type 2 diabetes and it is associated with the insulin resistance. Like the, type 1 diabetes it is also characterized by the high level of blood sugar o hyperglycemia. The onset of type 2 diabetes mellitus is associated with the lifestyle of the patient and as well as genetical inheritance is also one of the key reason of the disease. In this report, insulin synthesis and binding to its specific receptor, medicines of the disease that can be used in this scenario, and along with this control of the diabetes mellitus is also discussed.
Response to question.1
Insulin is synthesized in the beta cells of pancreas and at first a primary compound named preproinsulin is synthesized and then the its signal peptide is removed to produce proinsulin. Proinsulin is composed of three domains- an amino-terminal B chain, a carboxy-terminal A chain and a connecting peptide in between them as a C peptide. Within the, the endoplasmic reticulum , the C-peptide is excised and complete insulin is produced. After that, when beta cells are stimulated the hormones are secreted and by the exocytosis process and releases into the blood. The excised C-peptide is also released but there function is still unknown (Fu, Gilbert & Liu, 2013). When blood glucose level are in homeostasis condition, the signal is sent to the hypothalamus and a negative feedback mechanism stops the secretion of the insulin. At first insulin binds to the membrane receptor that is composed of two subunits. Insulin binds to the alpha subunit and causes a conformational change in the beta subunit of the receptor. The phosphorylated beta subunit causes activation of the protein kinase and makes the cells more permeable to the glucose. By increasing  the  glucose permeability, insulin helps in lowering the blood glucose level. In a study, it is seen that, depletion of IRS receptor can cause the insulin resistance and the defect in IRS-2 gene can cause diabetes(Boucher,  Kleinridders, & Kahn, 2014). In diabetes the insulin binds with the receptor, but there is no conformational in the receptor. As a result, the signal is not transmitted and glucose is not uptaken by the cell. This ultimately causes hyperglycemia. In this case, Jackson has  problem in insulin receptor that is in spite of  having adequate amount of insulin in the blood , the hormone cannot  bind to the proper receptor and as a result the glucose is not uptaken by the cell. As Jackson’s father had a history of DM II, the genetical defect in the insulin receptor genes (IRS I and IRS II) is responsible for this disease in him. In a healthy, non-diabetic patient, there is no defect in those genes and the receptors are properly helps to bind the hormones. So the conformational changes  in  the receptors helps in uptaking the blood glucose and maintains  the homeostasis. 
 Diabetic neuropathy refers to the damage of the nervous tissues by diabetes and it only happens in the persons who are suffering from the diabetes for a long period . In  addition to this, overweight, high blood pressure are also major causative factor for the neuropathy. There are mainly four type of neuropathy and they are peripheral, focal, autonomic and proximal neuropathy. In autonomic neuropathy the internal organ controlling nerves are mainly damaged and it is associated with alteration in heart rate , digestive system, blood pressure and problem in eyes(Smith, & Singleton, 2013).  Another common long term effect of DM II is  myocardial infraction. In diabetes mellitus, the atherosclerosis plaque formation and thrombosis  are  increased and it causes delaying in the treatment of the DM II (Chung et al., 2014). In this case of Jackson, it is seen that Jackson had a high blood pressure and overweight. Those two factors are responsible for the neuropathy. Along with this, he also had a high blood pressure, which is another sign of the neuropathy. As Jackson had a high blood pressure,he may have a plaques in his blood vessels due to the Diabetes II. This can cause myocardial infarction in future  due to plaques deposition in the blood vessels. 
 The Drug that can be used for the management of type II diabetes mellitus that is appropriate for the client and its mechanism of action:
In order to manage diabetes and its related complications for the patient, Metformin can be used as a safe medication for the patient. This medication is generally the first onbe to be prescribed and has been considered to be one of the safest. The medicine helps to improve the sensitivity of the body tissues to the effect of insulin and therefore helps the tissues to react to insulin in a more effective manner. It does so by helping the insulin to bind to its receptors on the cell. This therefore directly counteracts one of the key causes of type 2 diabetes in which the body grows insulin resistance, due to which the tissues stop reacting to it, and even though the body has enough concentration of insulin in blood, the body is unable to utilize it thereby causing diabetes. Additionally, Metformin helps to reduce the production of glucose in the liver by interfering in the biochemical pathway for glucose production from glycogen, thus helping to reduce the level of blood sugar, which is another aspect of diabetes which needs to be managed for the patient. Since high blood sugar leads to the adverse effects associated with diabetes, it management is crucial for diabetes treatment (Syngelaki et al., 2016).
Studies have also shown that conditions such as visceral adiposity among overweight and obese people are one of the most significant causes of insulin resistance and therefore diabetes. Therefore among patients suffering from insulin resistance should be first helped to overcome the resistance of the body tissues, along the target receptors on the cell to bind to insulin (Syngelaki et al., 2016; Nadeau et al., 2015). Due to this Metformin is usually the drug of choice for patients who are overweight or obese and have visceral adiposity or hyperglycemia, as seen in the case study. Additionally, since the the patient has a normally functioning pancreas, his insulin concentration in the blood is normal, because of which using insulin for the treatment will not be appropriate or effective since the patient already has insulin resistance. 
Insulin resistance can occur in a person with increased abdominal adiposity. Explain the pathophysiological basis for this.
Abdominal Adiposity or Visceral Adiposity is a condition in which there is an excessive deposit of adipose tissues also known as fat in the abdominal region and around the abdominal organs including the liver. Because of these fat deposits, the cells can develop insulin resistance as the receptors of insulin gets blocked and insulin can no longer bind to them. Studies have shown that visceral adiposity can lead to an increase in lipolytic activity, reduce the levels of adiponectin in the tissues, increase resistance to leptin and also increase the levels of inflammatory cytokines in the body. This is found to be the most significant in case of the deposition of fats on the liver causing the up regulation of the lypogenic pathway and causing impairment in the cell signaling process and hyperinsulenemia. These factors eventually cause an increase in the resistance of insulin in the body. Additionally, due to the presence of fats the re uptake of fatty acids in the liver also gets affected (Ryder et al., 2016). 
Explain why HbA1c is used a measure of long-term control of blood glucose levels and how this measure will be useful in the management of your person’s/client’s disease.
HbA1c is a type of hemoglobin, called the glycosylated hemoglobin which is used to measure the three month average blood or plasma concentration of glucose. The test can only measure a three month average for blood glucose, mainly because the life span of RBC is limited to four months. This is an effective strategy for the measurement of the level of glucose in the plasma, as it can help in the estimation of the amount of glucose molecules bound to the red blood cells. When there is an excessive amount of glucose in the body or an ineffective removal of glucose (due to insulin resistance), the glucose molecules starts to stick to the red blood cells as it travels through the circulatory system and the hemoglobins pick up the glucose due to a non enzymatic glycation pathway. This test would be useful for the patient as it can help to understand the glucose levels of the last three months and also assess the risks of cardiovascular problems due to diabetes (Wei et al., 2014).
Conclusion
Lastly, it can be concluded that DM II is a serious disease and the mechanism of the insulin secretion and problems of diabetes mellitus type 2 is discussed in this report. Along with this, the long term consequences and medicines of the disease that can be used in this situation is also discussed. 
Annotated bibliography:

Boucher, J., Kleinridders, A., & Kahn, C. R. (2014). Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harbor perspectives in biology, 6(1), a009191.

The purpose of selecting this article is to understand the signaling pathways of the insulin receptor in normal and insulin resistance states that is imposing impact on type 2 diabetes.  It has been known from the article that insulin signaling regulates glucose, lipid, and energy homeostasis, predominantly via action on liver, skeletal muscle, and adipose tissue. The positive as well as the negative modulators that act on different steps of the signaling pathway ensure a appropriate biological response to insulin in several tissues. It has been found that two chief phenomenon causes insulin resistance in human body. Firstly genetic mutations posses the potential to result in rare as well as severe insulin resistance, obesity has the potential to lead to insulin resistance through a variety of mechanisms.

Chung, S. C., Gedeborg, R., Nicholas, O., James, S., Jeppsson, A., Wolfe, C., … & Jernberg, T. (2014). Acute myocardial infarction: a comparison of short-term survival in national outcome registries in Sweden and the UK. The Lancet, 383(9925), 1305-1312.

This article has been chosen in order to assess time trends as well as outcomes in Sweden as well as Uk associated with acute myocardial infarction. It has been found that the international research for acute myocardial infarction is deprived of appropriate comparison of whole health systems. For research purpose, data from national registries on consecutive patients registered has been used. The researchers have also compared the effectiveness of the treatment  by using indirect casemix standardization. Finally it has been found that clinically crucial differences prevail between the countries when it comes to acute myocardial infarction care.

Fu, Z., R Gilbert, E., & Liu, D. (2013). Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Current diabetes reviews, 9(1), 25-53.

The purpose of selecting this article is to review the knowledge about the procedure by which beta cells synthesizes as well as secret insulin.  Pancreatic beta cell dysfunction plays a major role in formation of both type one as well as type 2 diabetes. Insulin that is secreted from beta cell is a critical regulator of metabolism. Hence it can be understood that insulin plays a major role in preventing the above mentioned disease. From the research, it has been concluded that both genetic as well as environmental factors posses the potential to lead to hyperglycemia, dyslipidemia, aautoimmunity and inflammation. All these, in turn, posses the potential to cause beta cell dysfunction and thus trigger the pathogenesis of diabetes.

Nadeau, K. J., Chow, K., Alam, S., Lindquist, K., Campbell, S., McFann, K., … & Walravens, P. (2015). Effects of low dose metformin in adolescents with type I diabetes mellitus: a randomized, double?blinded placebo?controlled study. Pediatric diabetes, 16(3), 196-203.

The purpose off selecting this article is to assess the effect of low dose metformin in adolescents who are suffering from type 1 diabetes mellitus. According to researchers,  tendency of the body to resist insulin increases during the period of adolescence within an individual who are suffering from type 1 diabetes. This phenomenon imposes adverse effect on the body of the individuals by complicating glymic control along with increasing the chance of cardiovascular diseases. In order to minimize the issue, healthcare service users should take low dose metformin in order to enhance BMI as well as insulin sensitivity.  

Ryder, J. R., Dengel, D. R., Jacobs Jr, D. R., Sinaiko, A. R., Kelly, A. S., & Steinberger, J. (2016). Relations among adiposity and insulin resistance with flow-mediated dilation, carotid intima-media thickness, and arterial stiffness in children. The Journal of pediatrics, 168, 205-211.

The objective of this research paper is to determine the associations of adiposity as well as insulin resistance with measures of vascular structure as well as function in children. After conducting this research, it has been found that FMD is positively associated with high adiposity. On the other hand insulin resistance posses no direct relation with FMD. Along with that carotid intima-media thickness is directly associated with obesity, VAT as well as insulin resistance. From the findings of the research, it can be concluded that adiposity is related to higher FMD and insulin resistance is directly proportional to higher cIMT in children. However, further research is necessary in order to gain progress  of the mentioned relations.

Smith, A. G., & Singleton, J. R. (2013). Obesity and hyperlipidemia are risk for early diabetic neuropathy. Journal of Diabetes and its Complications, 27(5), 436-442.

The purpose of this research paper is to find out  how obesity as well as hyperlipidemia are risky for early diabetic neuropathy. In this article the relation between gycemic control, lipid parameters, blood pressure and neuropathy is examined. Significant relationship between these feature ans nuropathy has been observed. Finally, it has been found that obesity as well as hypertriglyceridemia  posses the potential to enhance the risk for peripheral neuropathy, irrespective of the glucose level in the body. On the other hand, obesity as well as hyperglysemia have differential effects on tiny and large fibers.

Syngelaki, A., Nicolaides, K. H., Balani, J., Hyer, S., Akolekar, R., Kotecha, R., … & Shehata, H. (2016). Metformin versus placebo in obese pregnant women without diabetes mellitus. New England Journal of Medicine, 374(5), 434-443.

The purpose of this article is to find out which whether metaformin or placebo is beneficial for obese pregnant women without diabetes mellitus. Obesity posses direct linkage with enhanced risk of adverse pregnancy outcomes. Several lifestyle intervention studies have shown enhanced outcomes. Metamorphin enhances the sensibility in pregnant patients who have gestational diabetes. It has been found that among women without diabetes who posses  a BMI of more than 35, the antenatal administration of metformin reduced maternal weight gain but not neonatal birth weight. 

Wei, N., Zheng, H., & Nathan, D. M. (2014). Empirically establishing blood glucose targets to achieve HbA1c goals. Diabetes Care, DC_132173.

The purpose of thus research article is to determine the average fasting, postprandial as well as bettime self monitored blood glucose concentrations related to specific hbA levels using data. It has been found that the average BG premeal, postmeal, and at bedtime to achieve a variety of HbA1c targets. These results, based on empirical data, will help patients and providers set realistic day-to-day SMBG targets to achieve individualized HbA1c goals.

Koffert, J. P., Mikkola, K., Virtanen, K. A., Andersson, A. M. D., Faxius, L., Hällsten, K., … & Virta, J. (2017). Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial. diabetes research and clinical practice, 131, 208-216.

The study outlined by the respective  authors,  utilized human subjects for the study.  The  sample size of the  concerned research  selected a total number of forty five patients who were  inflicted with  diabetes mellitus,  pertaining to the type 2, uncontrolled type. The concerned patients were also  not under any  previously recommended medications of the  antibiotic category. Of these two patients part of the  previous selection  had to undergo exclusion  due to their adherence to medications such as metformin and rosiglitazone.  There was further a lack of  recording of  follow  up information  from patients adhering to the  usage  of  placebo  and rosiglitazone.   The  respective  research   was approved by  the  committee  dealing with ethical issues  pertaining to the  conductance of research, situated at the  local  level.   Hence, a  total of patients amounting to a sample size of forty one were selected by the author for the concerned research, comprising of a randomized, double blind trial. The time span of the concerned research was twenty six weeks. The aforementioned patient group was divided into three subgroups, pertaining to the usage of placebo, rosiglitazone and placebo usage. During the occurrence of euglycemia hyperinsulemia, the uptake of glucose pertaining to the tissue level was assessed with the aid of FDG PET, prior to the commencement of the medication treatment, as well after the ingestion of the aforementioned substances. 
References:

Boucher, J., Kleinridders, A., & Kahn, C. R. (2014). Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harbor perspectives in biology, 6(1), a009191.
Chung, S. C., Gedeborg, R., Nicholas, O., James, S., Jeppsson, A., Wolfe, C., … & Jernberg, T. (2014). Acute myocardial infarction: a comparison of short-term survival in national outcome registries in Sweden and the UK. The Lancet, 383(9925), 1305-1312.
Fu, Z., R Gilbert, E., & Liu, D. (2013). Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Current diabetes reviews, 9(1), 25-53.
Nadeau, K. J., Chow, K., Alam, S., Lindquist, K., Campbell, S., McFann, K., … & Walravens, P. (2015). Effects of low dose metformin in adolescents with type I diabetes mellitus: a randomized, double?blinded placebo?controlled study. Pediatric diabetes, 16(3), 196-203.
Ryder, J. R., Dengel, D. R., Jacobs Jr, D. R., Sinaiko, A. R., Kelly, A. S., & Steinberger, J. (2016). Relations among adiposity and insulin resistance with flow-mediated dilation, carotid intima-media thickness, and arterial stiffness in children. The Journal of pediatrics, 168, 205-211.
Smith, A. G., & Singleton, J. R. (2013). Obesity and hyperlipidemia are risk factors for early diabetic neuropathy. Journal of Diabetes and its Complications, 27(5), 436-442.
Syngelaki, A., Nicolaides, K. H., Balani, J., Hyer, S., Akolekar, R., Kotecha, R., … & Shehata, H. (2016). Metformin versus placebo in obese pregnant women without diabetes mellitus. New England Journal of Medicine, 374(5), 434-443.
Wei, N., Zheng, H., & Nathan, D. M. (2014). Empirically establishing blood glucose targets to achieve HbA1c goals. Diabetes Care, DC_132173.

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