NUR 631: Advanced Physiology and Pathophysiology Essay

High blood pressure, or most usually termed as hypertension is one of the most common diseases that affects the human population and approximately 1 billion individuals are afflicted by it and around 7.1 million deaths per year can be affiliated with it. (Chobanian, et al., 2003). However all these deaths are caused mostly by cardiovascular disease and another disease, death does not occur b hypertension on its own but by many of the acute linked diseases like Myocardia Infraction, strokes and renal failures. (Rodriguez-Cruz, 2009). As it is the leading cause of mortality and morbidity, it possesses important health challenge as the cost associated with treating it and reducing other risk factors associated with it a lot of active research is being done to understand the causes and the pathophysiology. NUR 631: Advanced Physiology and Pathophysiology Essay

Classification

Normal blood pressure is considered to be 115/75 mmHg, whereas the 115 is the systolic pressure (occurs during contraction of the ventricles) and 75 is the diastolic pressure (occurs during the relaxation of ventricles). (Oparil & Weber, Hypertension: A Companion to Brenner and Rector’s The Kidney, 2005). An individual is treated with hypertension when their blood pressure is consistently over 140/90 mmHg, however doctors these days are becoming more cautious and start treatment when the pressure touches 130/80 mmHg . It is known that cardiovascular risk increases for every 20/11 mmHg increment. (Chobanian, et al., 2003). NUR 631: Advanced Physiology and Pathophysiology Essay

Hypertension can be broadly classified into two groups; primary/essential and secondary hypertension. About 90 to 95% population diagnosed with hypertension has primary type, for which the cause is not full known and seems to be more prevalent as people age; it may increase up to 75% in people aged over 75. (Rodriguez-Cruz, 2009) (Carretero & Opari, 2000). Secondary hypertension is caused by an underlying medical condition which has altered the homeostatic pathway of regulating blood pressure. Secondary hypertension is more easily treatable as the underlying cause can be identified. Some commonly recognised diseases that may cause hypertension include Cushing’s disorder, kidney diseases and tumours. Another important cause is the genetic abnormality of the aorta. (Williams, 2010). NUR 631: Advanced Physiology and Pathophysiology Essay

Signs and Symptoms

Moderate hypertension which starts from 140/90 is asymptomatic. Prolonged and sudden enhanced blood pressure is linked to headaches, sleepiness and visual disturbances; which in turn can cause nausea. (McPhee, Papadakis, & Tierney, 2008)While it is known hypertension is more prevalent in elderly, children can be affected as well in the children the symptoms may be as more acute like epistaxis, and bell palsy. (Rodriguez-Cruz, 2009). Children usually exhibit hypertension due to some other underlying cause, and thus most cases are of secondary nature. (Rodriguez-Cruz, 2009).The signs and symptoms of secondary hypertension are dependent upon the ailment that is causing it and thus the indicators for Cushing’s syndrome would be different from the genetic one or drug induced one. (Williams, 2010). NUR 631: Advanced Physiology and Pathophysiology Essay

Pathophysiology

The exact cause of the primary hypertension is not known. There are many risk factors including age, genetics, metabolic, race and “sedentary lifestyle which can cause obesity” and it has been estimated that 85%of the cases of hypertension have a higher BMI than 25. (Haslam & James, 2005)

Figure 1: This figure shows the key elements of the pathophysiology of hypertension and all the risk factors which increase the likelihood of contracting the ailment. Abbreviations used here: AME- apparent mineralocorticoid excess; CNS – central nervous system; GRA – glucocorticoid-remediable aldosteronism. (Oparil, Zaman, & Calhoun, Pathogenesis of Hypertension, 2003). NUR 631: Advanced Physiology and Pathophysiology Essay

The pathophysiologic mechanism and the vascular irregularities are speculative and it is actively being researched upon. Blood pressure is the combined consequence of cardiac output and vascular resistance thus either one can independently or in combination cause hypertension. (Dreisbach & Sharma, 2010). Different studies show that several factors may work independently or together to turn the neurohumoral systems on or off. In patients with a hyper-responsive system due to “changed vascular properties” an aggravated pressure flow is observed. (Randal, 1991). It has also been studied that there is a natural evolution of the disease thus man researchers suggest the one of the reason of the early elevations of the blood volume or the cardiac output may be the inadequate elimination of sodium by kidneys. Increased sodium levels can increase the osmotic pressure hence the blood volume. It chronic hypertension subjects the cardiac output and the blood volume is usually close to the normal. So it can be inferred that hypertension is maintained by the increase in vascular resistance by a decrease of elasticity of the walls as in aging or “by a reduction in lumen Diameter” (Khabunde, 2007) when the individual has been following a medically unhealthy lifestyle. These “changes in arterioles, which increase total peripheral resistance, result in an increase in diastolic and a secondary increase in systolic blood pressures” (Randal, 1991). NUR 631: Advanced Physiology and Pathophysiology Essay

Another factor that different studies have showed relate the decrease in sensitivity of receptors of the receptors in the vessels The decrease in receptors sensitivity modifies central nervous system (CNS) manipulation of sympathetic nervous system (SNS) distribution, resulting in two expressions. First, having an insensitive receptor requires a larger change in blood pressure to produce the same response as the receptor doesn’t get activated. Secondly decreased receptors “sensitivity results in enhanced SNS activity for a given level of arterial blood pressure.” (Supiano, 2001)

In hypertension there is has been shown evidence that changes in vascular endothelial function (VEF) can hamper normal vascular tone of hypertensive patients. Vascular tone can be changed by increase circulation of angiotensin II, or by the increased sympathetic activity (as discussed above). The altered sympathetic activity can lead to a decrease in production of nitric oxide which is a vasodilator or endothelin production could increase, which is a vasoconstrictor. (Khabunde, 2007). Type 2 diabetes can causes endothelial dysfunction “by enhanced oxygen free radical-mediated damage and decreased nitric oxide bioavailability.” (Khabunde, 2007). NUR 631: Advanced Physiology and Pathophysiology Essay

Other factors that maintain hypertension are caused by dysfunction in electrolyte homoeostasis especially deviations in sodium, calcium, and potassium concentrations. Sodium example has been already discussed above. In addition, calcium increases vascular contractility. It can also stimulate renin release; the same mechanism is thought to operate in obesity-mediated hypertension. Renin synthesis epinephrine, and activity of the sympathetic nervous system, which can be linked back to abnormalities seen in vascular tone. Potassium, however, helps decrease the blood pressure as it suppresses the release of renin. (Rodriguez-Cruz, 2009). NUR 631: Advanced Physiology and Pathophysiology Essay

This figure explains the different factors that directly affect the blood pressure, which is later affected by other different factors. In hypertension cardiac output is usually normal and therefore peripheral resistance sustains hypertension by the dysfunction in vascular function or decreases in lumen by a sedentary lifestyle. The figure is taken from Wikipedia. (Wikipedia, 2009)

It can be seen the complexity of the system, as many mechanism works to sustain hypertension. In different individuals, it can be difficult to understand which systems are operational thus designing treatments can be difficult, and treatments are then usually more often designed to affect the regulatory factors rather than cause. (Randal, 1991). NUR 631: Advanced Physiology and Pathophysiology Essay

Treatment

Treatment usually works to regulate the factors which maintain hypertension. Non-pharmacological treatments include lifestyle changes like decrease/halt in alcohol and cigarette consumption and if needed weight reduction with a more active lifestyle. Caffeine intake is also minimized as it increases the pulse rate. It is assessed that lifestyle interventions can reduce blood pressure by at least 10 mmHg in about 1 in 4 people with high blood pressure. (Association, 2009).Yet most of the times pharmacological interventions are used as they more affectively regulate blood pressure, there around 6 classes of pharmacological medications available which all perform at different levels to bring the blood pressure to normal. (Oparil & Weber, Hypertension: A Companion to Brenner and Rector’s The Kidney, 2005). NUR 631: Advanced Physiology and Pathophysiology Essay

• ACE inhibitors: inhibits the assembly of angiotensin II, as a result, the vessels expand improving the blood flow. The tension in the circulation is regulated to normalcy by increase filtration by the kidneys. The decrease in levels of fluids also helps reduce blood pressure. This medication is used only when other medications are not working.
• Angiotensin-II receptor antagonists: they work in an analogous manner to ACE inhibitors. However, instead of stopping the production of angiotensin II, they prevent its action on the receptors. Again vessels are able to expand, improving blood flow and reducing blood pressure.
• Beta-blockers block the effects of sympathetic nervous system and the hormone epinephrine. This decreases the cardiac output as it relaxes the heart so the pulse rate is slowed down, lowering the blood pressure.
• Alpha-blockers: triggers the vessels to ease and expand. Giving them in combination with beta-blockers has a greater effect.
• Calcium-channel blockers: expand the arteries to reduce the muscle tension and also decrease the cardiac output by relaxing the heart muscles so it pumps more slowly, reducing blood pressure. NUR 631: Advanced Physiology and Pathophysiology Essay
• Diuretics: help clear the unnecessary sodium and water thru kidneys, which decrease the osmotic pressure. They also relax the blood vessels reducing the strain on them. (Uren & Rutherford, 2004)

Treatment for hypertension is throughout one’s life as hypertension is not curable; however, all the drug classes above help maintain the blood pressure quite well within the normal range.

Summary

The complexity of pathophysiologic mechanisms that lead to high blood pressure is such that selective antihypertensive treatment is rarely possible and a number of drugs and lifestyle changes are required to bring any change. Hypertension is widespread among middle-aged and elderly and controlling their blood pressure is a challenge we face as we still have not properly understood the underlying causes of primary/essential hypertension. (Oparil, Zaman, & Calhoun, Pathogenesis of Hypertension, 2003). NUR 631: Advanced Physiology and Pathophysiology Essay

Bibliography

• Association, B. P. (2009, March 4). High Blood Pressure. Retrieved March 8, 2010, from Patients UK: http://www.patient.co.uk/health/High-Blood-Pressure-(Hypertension).htm
• Carretero, O. A., & Opari, l. S. (2000, Jan 25). Essential hypertension. Part I: definition and aetiology. Circulation, 3(101), 329-335.
• Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., et al. (2003, December 1). Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension, 42, 1206-1252.
• Dreisbach, A. W., & Sharma, S. (2010, Feb 19). Hypertension and Kidney. Retrieved March 8, 2010, from Emedicine: http://emedicine.medscape.com/article/241381-overview
• Haslam, D., & James, W. (2005). Obesity. The Lancet, 366, 1197-1209.
• Khabunde, R. E. (2007, January 04). Primary (essential) hypertension. Retrieved March 8, 2010, from Cardiovascular Physiology Concepts: http://www.cvphysiology.com/Blood%20Pressure/BP024.htm
• McPhee, S. J., Papadakis, M. A., & Tierney, L. M. (2008). Current Medical Diagnosis and Treatment 2008. United States: McGraw-Hill. NUR 631: Advanced Physiology and Pathophysiology Essay
• Oparil, S., & Weber, M. A. (2005). Hypertension: A Companion to Brenner and Rector’s The Kidney (2nd ed.). United States: Elsevier.
• Oparil, S., Zaman, M. A., & Calhoun, a. D. (2003). Pathogenesis of Hypertension. PHYSIOLOGY IN MEDICINE: A SERIES OF ARTICLES LINKING MEDICINE WITH SCIENCE, 761-776.
• Randal, l. O. (1991). Physiology and pathophysiology of hypertension. Journal of the Association for Academic Minority Physicians, 151-155.
• Rodriguez-Cruz, E. (2009, Nov 16). Hypertension. Retrieved March 8, 2010, from eMedicine: http://emedicine.medscape.com/article/889877-overview
• Supiano, M. A. (2001, Dec 2). Hypertension: Classification, Epidemiology, Diagnosis, Evaluation and Treatment. Retrieved March 8, 2010, from Armenian Health Network: http://www.health.am/hypertension/hypertension/#Pathophysiology
• Uren, N., & Rutherford, D. (2004, Sept 24). High blood pressure (hypertension). Retrieved March 8, 2010, from Net Doctor: http://www.netdoctor.co.uk/diseases/facts/hypertension.htm
• Wikipedia. (2009, June 8). Arterial Pressure. Retrieved March 8, 2010, from Wikipedia: http://en.wikipedia.org/wiki/File:Arterial_pressure_diagram.png
• Williams, B. (2010, Feb 10). Secondary Hypertension. Retrieved March 8, 2010, from Hypertension: Overview, Causes, Symptoms, Risk factors, Treatment: http://www.health.am/hypertension/secondary-hypertension/ NUR 631: Advanced Physiology and Pathophysiology Essay

George Huntington first described Huntington Disease in 1872 as “coming on gradually but surely, increasing by degrees, and often occupying years in its development until the hapless sufferer is but a quivering wreck of his former self” (Visser, 2010). Huntington disease is an inherited genetic disorder, which causes the progressive degeneration of selected nerve cells in the brain. This degeneration of nerve cells results in impairment of both mental capability and physical control which results in death (Visser, 2010). This essay will look at the pathophysiology of Huntington disease in relation to the possible signs and symptoms. While also identifying the risk factors and examining the relevant tests available with regards to screening, diagnosing and monitoring treatment within New Zealand. It will then further explore the treatment options available in New Zealand and treatment developments worldwide. NUR 631: Advanced Physiology and Pathophysiology Essay

Pathophysiology of Huntington disease in relation to signs and symptoms

Huntington disease is caused by a genetic fault in a small section located on chromosome 4, which encodes a protein called Huntington (Porth, 2011). However, the function of the Huntington protein is still unknown, yet this protein appears to be important to neurons in the brain (Visser, 2010). This genetic fault results in a segment of DNA, known as a CAG trinucleotide repeat, this segment of DNA is made up of a series of DNA building blocks cytosine, adenine and guanine that appear multiple times in a row (Visser, 2010). The normal copy of this gene contains 6 to 35 copies of the trinucleotide repeat, compared to the faulty gene which contains 40 to 120 copies of the trinucleotide repeat resulting in this gene producing an expansion of Huntington’s gene (Porth, 2011). The larger number of trinucleotide repeats is generally associated with an earlier onset of Huntington’s’ disease. This is shown as adults with Huntington’s disease generally have 40-50 trinucleotide repeats where people with the juvenile form of this disorder tend to have more than 50 trinucleotide repeats (Visser, 2010). Also, Visser (2010) suggests that due to the elongation of the CAG trinucleotide segment, the segment gains a toxic function that disrupts the normal function of neurons and eventually leads to the death of neurons. NUR 631: Advanced Physiology and Pathophysiology Essay

Cells are known as building blocks of life that use energy to carry out biological functions, while also producing oxidants that can potentially damage themselves; Yet, these cells can make such chemicals harmless (Visser, 2010). Current studies suggests that the protein Huntington somehow prevents the brain cells from protecting themselves against the toxic chemicals which results in Huntington’s disease causing the localized death of brain and spinal cord cells (Porth, 2011). Basal ganglia are the first neurons to be affected by Huntington disease; these neurons are associated with a variety of functions that modulate motor movements, emotions, cognitive and learning abilities (Porth, 2011). Therefore the deteriation of basal ganglia results in many symptoms which commonly occur around 35 and 55 years of age, however these symptoms will progressively get worse which results in the individual passing away in around 10-20 years (Porth, 2011). NUR 631: Advanced Physiology and Pathophysiology Essay

There are early signs and symptoms of Huntington disease which include uncontrolled muscular movements, memory problems and mood changes (Visser, 2010). Yet, these symptoms quickly develop into serious motor impairment conditions such as eye movement disorders, spasticity, dysphagia, dysarthria, myoclonus, and the main impairment chorea which involves rapid, jerking movements that the individual has no control over (Porth, 2011). As Huntington disease develops it results in a cognitive decline, mental slowing which is the inability to remember people and to make decisions for oneself (Porth, 2011). This can all eventually lead to dementia. There are many factors that influence behavioural symptoms which include stress about the disease, family relationships, and as the pathways through the basal ganglia become disconnected which results in a loss of frontal lobe functions (Visser, 2010). The major behavioural symptom is depression with 30% of individuals with Huntington disease experiencing major depressive or dysthymic disorders and 6% resulting in suicide (Porth, 2011). Other behavioural symptoms such as personality changes results in the individual appearing to have no interest in life or the individual having increased anger and irritability which further links to impulsive actions and violence, these actions can cause stress in relationships between family members (Visser, 2010). NUR 631: Advanced Physiology and Pathophysiology Essay

Risk Factors of Huntington disease

Everyone receives two copies of each gene which are singularly known as alleles, one from each parent, that are present in all cells of the body (Lemiere, 2004). Therefore most individuals are born with two normal copies of each allele (Lemiere, 2004). However in the case of hereditary disorders specifically Huntington’s disease, an individual is born with one normal gene and a gene defect which is called a mutation (Lemiere, 2004). Huntington disease has an autosomal dominant inheritance pattern which means that a child of a parent who carries the mutation has a 50% chance of inheriting the mutation (Frank, 2014). If the child inherits the mutation the child will develop Huntington’s disease some point in the individual’s life, and can also pass it on to their children. But if the individual does not inherit the mutation then they cannot pass it on to their children (Frank, 2014). Yet, there are also rare cases where individuals develop Huntington’s disease, without a family history of the condition (Visser, 2010). This generally happens because of a genetic mutation during the father’s sperm development (Visser, 2010). NUR 631: Advanced Physiology and Pathophysiology Essay

However, there is a process where fertilized embryos can be tested for Huntington’s disease prior to the embryos being implanted within a mother’s womb called pre-implantation genetic diagnosis (Christian, 2007). This technique allows the parent that carries the Huntington’s disease to avoid passing the genetic condition to their children (Christian, 2007). Pre-implantation genetic diagnosis is completed through in-vitro fertilization (IVF) where the mother’s egg is fertilized with the father’s sperm outside the body (Christian, 2007). The eggs then develop into embryos, after three days of being cultured in the laboratory the technique of embryo biopsy is performed, this test checks the embryo for the Huntington’s disease and therefore all the embryos are then implanted back into the mother (Christian, 2007). New Zealand has been ethically approved for pre-implantation genetic diagnosis however this is only under special circumstances (Christian, 2007). The government only funds pre-implantation genetic diagnosis for 40 couples a year with one single attempt at pregnancy; this funding includes all serious genetic conditions (Christian, 2007). NUR 631: Advanced Physiology and Pathophysiology Essay

Relevant diagnostic, screening and monitoring tests in New Zealand

Genetic tests are an example of a diagnostic as it is a procedure performed that establishes if an individual has the presence or absence of Huntington’s disease (Lyon, 2013). Individuals that have symptomatic symptoms of Huntington’s disease may be recommended by health care professionals to undertake a genetic test for the faulty Huntington gene (Visser, 2010). However, there is also predictive DNA testing which is for asymptomatic individuals with a 50% chance of developing Huntington’s disease, these individuals are tested to see if they will be affected or not by the faulty gene in adulthood (Visser, 2010). Both of these genetic tests are accomplished in the same way and can be done in Auckland laboratory (Lyon, 2013). Genetic testing is done by DNA being extracted from the individual’s blood sample, and then the DNA being purified (Lyon, 2013). A technique called polymerase chain reaction is then implicated to locate the two Huntington genes, once found millions of exact copies are made for further analysis (Lyon, 2013). This further analysing is when the DNA is sorted by size to determine the number of CAG repeats in each gene. The three outcomes to the test are based on the CAG repeats (Lyon, 2013). If an individual receives a negative test it means the CAG repeat size is 30 or less and therefore the individual is not at risk of developing Huntingtons disease, but if an individual receives a positive test it means the CAG repeat size is 40 or more and the individual will develop Huntington’s disease generally in adulthood (Lyon, 2013). However if an individual receives uninformative it mean the CAG repeat is in the immediate range between 31-39 and is unclear if the individual will develop Huntington’s disease (Lyon, 2013). NUR 631: Advanced Physiology and Pathophysiology Essay

Other tests available are known as screening this is where a series of tests are used to predict the presence of disease in individuals at risk (Lemiere, 2004). These tests include neurological examinations, along with structural and functional imaging. Neurological examinations are performed by a neurologist, which intensively interviews an individual to obtain the medical history and rule out other possible medical conditions (Lemiere, 2004). Some key aspects neurologists use to identify Huntington’s disease include taking a family history as Huntington disease is an inherited disorder and taking note of reflexes, muscle strength and eye movements as some of the earliest manifestations of the disease are “subtle chorea, eye movement and fine motor abnormalities” (Lemiere, 2004). However, Lemiere (2004) suggests that the Huntington gene defect may influence brain function and behaviour during asymptomatic years, this research has been conducted using presymptomatic individuals who have a positive gene defect. These individuals had a volume reduction of “30.9% for the caudate, 29.3% for the globus pallidus and 25.7% for the putamen” (Lemiere, 2004) compared to individuals with a negative gene defect from offspring of Huntington disease patients (Lemiere, 2004). This research shows that the decline of basal ganglia occurs gradually before the onset of Huntington disease symptoms (Lemiere, 2004). Therefore healthcare professionals can use MRI and CT scans of the brain to help determine if patients have Huntington’s disease (Lemiere, 2004). NUR 631: Advanced Physiology and Pathophysiology Essay

The monitoring of treatment is extremely important in Huntington’s disease and dependently relies on the motor, behavioural and cognitive aspects of the individual (Frank, 2014). After the onset of Huntington disease the individuals’ functional abilities gradually worsen over time due to the Huntington gene mutation that causes a localized death of neurons which helped to regulate the motor movements, emotional and cognitive abilities (Frank, 2014). The loss of these abilities requires the individual to seek help for all activities of daily care, yet later in the disease the individual will be confined to a bed with the inability to speak (Frank, 2014). This gradual decline of the individuals’ condition makes it important for health care professional to monitor the individuals’ treatments and adjust the treatment accordingly to the disease progress (Frank, 2014). Further, the drugs used in treatment of Huntington’s disease has the potential to cause significant side effects that can worsen symptoms of the disease (Frank, 2014). Therefore it is critically important for health care professionals to monitor the risk- benefit ratio effect the treatment has on an individual (Frank, 2014). NUR 631: Advanced Physiology and Pathophysiology Essay

Treatment available in New Zealand and further treatment developments worldwide

Currently, there is no cure for Huntington disease, but medications, psychotherapy, speech and physical therapy can be implemented to help minimize symptoms while also allowing the individual to adapt to their condition (Frank, 2014). Medications to help treat movement disorders in New Zealand include Xenazine this medication helps to suppress chorea, but has possible side effects of aggravating depression (Frank, 2014). Also, the use of certain antipsychotic drugs such as haloperidol and clozapine can help alleviate choreic movements and further controlling hallucinations and violent outbursts, but the possible side effects can worsen dystonia and muscle rigidity (Frank, 2014). NUR 631: Advanced Physiology and Pathophysiology Essay

Due to the loss of frontal lobe functions as an effect of the disease, there needs to be increased psychiatric support for individuals with Huntington’s disease (Visser, 2010). This support can come from medications that support depression such as antidepressants which include fluoxetine, sertraline and esctislopram (Frank, 2014). This treatment of depression can further help to improve the symptoms of sleep disturbance, social withdrawal and lack of interest in general life (Frank, 2014). However, using antidepressants can include the side effects of insomnia, diarrhoea, nausea and sexual problems (Frank, 2014). Other medications to help individuals can be antipsychotic and mood stabilizing drugs which help to supress violent outbursts, highs and low mood swings, the common side effects of these medications include weight gain, tremor and gastrointestinal problems (Frank, 2014). NUR 631: Advanced Physiology and Pathophysiology Essay

Psychologists can provide talking therapy for an individual with Huntington disease, this therapy allows the individual to understanding the conditions effects, while further discussing the problems and feeling the individual has (Frank, 2014). Such problems the individual could be concerned about are talking, eating and swallowing this is because Huntington disease impairs the control of muscles of the mouth and throat (Frank, 2014). A speech therapist can address these issues and improve the individual’s ability of communication by implementation communication devices (Frank, 2014). Physical therapy is also an important part of Huntington disease as the exercises provide help improve strength, balance and coordination, which further results in the individual maintain mobility for as long as possible and minimizing the possible falls (Frank, 2014). NUR 631: Advanced Physiology and Pathophysiology Essay