Lecture notes, lectures 1-9 - Complete PDF

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Module 1: The Stress Response - Module 2: Alterations in Hormonal Regulation – Diabet - Module 3: Inflammation and Immunity - Module 4: Depression - Module 5: Fluid and Electrolyte Imbalances - Module 2: Alterations in Respiratory Function- Asthma - Module 3: Childhood Obesity - Module 2b: COPD - Mo...

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Patho- Module 1 The Stress Response

What is Stress? -Stress is a response, not something that happens to us. -There are external influences (or stressors) that alter your homeostatic balance. -The stressor, the stress response, and the pathophysiological sequelae.

THE STRESSORS -Stressors can be positive (Eustressors). -Stressors can be negative (Distressors). -Stressors can be neutral and these don’t necessarily lead to stress until we change them into a negative or positive stressor. EXTERNAL STIMULI -External stimuli are external demands that trigger reactions. - Stressors can be categorized into three different factors.

1. Quantity -negative consequences due to an accumulation of stressors -EX. Holmes and Rahe Stress Scale

2. Quality -could be a major change that affects a lot of people (wars or economic depression) -could be a major change that a affects few people (divorce) -could be a daily hassle

3. Duration -can be acute or time limited (job interview) -could be sequential (changes that follow divorce) -could be chronic-intermittent (periodic family arguments) -could be chronic

PHYSIOLOGICAL RESPONSE- three key areas 1. Perception or emotion- frustration, anger, and fear can lead to the hormonal release. 2. Primary Hormones involved are: -Glucocorticoids: mainly cortisol -Mineralcorticoids: primarily aldosterone -Catecholamines: epinephrine, norepinephrine, and a small amount of dopamine. 3. Consequences

BODY’S RESPONSE TO STRESS The Adrenal Glands (Retroperitoneal glands) -They are comprised of three main layers. 1. The outer layer is The Capsule. This is a tough, fibrous capsule enclosed in fat for protection.

2. The Adrenal Cortex forms the bulk of the gland and makes up 80-90% of the gland. This layer has three divisions or zones. a) Outer Layer: Zona Glomerulosa- this produces primarily aldosterone. 95% of the mineralocortecoid produced is in the form of aldosterone. This is key for regurgitating sodium and potassium secretion and retention. Aldosterone is the key component of the renninangiotensin aldosterone pathway for volume and blood pressure control. Aldosterone plays a role with the pH balance, as it facilitates the excretion of hydrogen ions. If someone has too much aldosterone excreted (aldosteronism), it is usually related to the neoplasms (an abnormal

mass of tissue that results when cells divide more than they should or not die when they should). The person will present with hypertension, and edema due to the high sodium. A decrease in potassium will cause muscle weakness or paralysis. If too little aldosterone is secreted, it can lead to hypotension. Dehydration can be common, decreased sodium, increased potassium, and potential weight loss. b) Middle Layer: Zona Faciculate- 95% of the gluco-corticoid secreted is in the form of cortisol. Cortisol is released with ATCH (adrenocorticotrophin) stimulation and there is negative feedback with increased cortisol levels. Adrenocorticotropic hormone is made in the corticotroph cells of the anterior pituitary gland. It is secreted in several intermittent pulses during the day into the bloodstream and transported around the body. Once adrenocorticotropic hormone reaches the adrenal glands, it binds on to receptors causing the adrenal glands to secrete more cortisol, resulting in higher levels of cortisol in the blood. Cortisol, also known as hydrocortisone is the major stress hormone. It is important to understand that cortisol is secreted during periods of stress and it is essential for our survival. Cortisol increases blood glucose by decreasing peripheral uptake and promoting gluconeogenesis. It acts synergistically with glucagon and epinephrine. It decreases insulin sensitivity. This should help understand why well controlled diabetes are harder to control in the hospital setting and their control often improves when they go home. It increases protein synthesis in the liver but also promotes the catabolism (breakdown) in the muscles. Cortisol promotes lipolysis in the extremities and there seems to be important acute and long term effects on the fatty acid breakdown. In the acute stage, cortisol promotes the breakdown of fatty acids to be used as a source of energy. However in the long term with sustained cortisol levels, the body starts to redistribute fat or promote lipogenesis in the face and trunk area (Cushingoid signs). Another key role of cortisol is that it’s an anti-inflammatory and an immunosupression. Cortisol Effects: Insufficient Cortisol Addison’s disease Excessive Cortisol Cushing’s disease

c) Inner Layer: Zona Reticularis- Gonadocorticoids are made here. They are considered very weak androgens. Primarily DHEA (dehydroepiandrosterone) and DHEA sulphate can be converted to testosterone or in females, estrogen. If too much DHEA is secreted, it can lead to an increase in facial hair. (PCOS- polycystic ovarian syndrome).

3. Lastly the innermost layer is the Adrenal Medulla, which is more like a knot of nervous tissue and is part of the sympathetic nervous system accounting for 10-20% of the gland. The Adrenal Medulla is made up of chromaffins cells called pheochromocytes. It has a rich blood supply and a rich nerve supply. Epinephrine and norepinephrine are secreted and epinephrine is 10 times more potent here. Adrenal Medulla also has key links to the autonomic sympathetic(fight or flight) nervous system.

Adrenal Gland Hormones Summary

PHYSIOLOGICAL RESPONSE: HPA (HYPOTHALAMIC-PITUITARY-ADRENAL) AXIS

-Stressors activate the limbic system and parts of the cerebral cortex, to ultimately stimulate the hypothalamus. HYPOTHALAMUS -

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The hypothalamus is the clearing house for many homeostasis controls. It releases corticotrophin releasing hormone, and this stimulates the sympathetic nervous system by the locus ceruleus. When CRH is released, it stimulates the Anterior Pituitary to release ACTH (adrenal corticotropic hormone). ACTH is responsible for releasing cortisol from the adrenal gland SIDE NOTE: Cortisol, the stress hormone is essential for general adaptation to stress in the body, and plays a crucial role in cardiovascular, metabolic, and immunological balances. As it circulates in the blood, most 90-95% is bound to the cortisol-binding

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globulin and a small amount is bound to albumin. This protects the cortisol from being cleared in the liver, but it must become unbound to be physiologically active. When activated by stress, the hypothalamus also stimulates the locus ceruleus. This area located in the brain stem is the integrating centre for the autonomic nervous system, as norepinephrine is synthesized here. In response to stress, after norepinephrine is synthesized, it goes from the locus ceruleus by the afferent pathways back to the hypothalamus limbic system, hippocampus and cerebral cortex. When the sympathetic nervous system is activated, it releases epinephrine and norepinephrine from the adrenal gland. These catecholamines allow the body to support increases physical activity and rapid production of ATP. Epinephrine will increase the glucose available in the body by gluconeogenesis and this will limit the uptake of peripheral glucose, plus will also limit the pancreas’ production of insulin resulting in hyperglycemia. Epinephrine also causes broncho-dilation, promote lipolysis, and increase heart rate. Other hormones are also released from the anterior pituitary in response to hypothalamic stimulation. a) Beta endorphins- increased levels reduce pain sensations. b) Prolactin- released during stress c) Growth hormone- increases amounts affect protein, lipid, and carbohydrate metabolism and also counters the effects of insulin.

-The stimulation of the Posterior Pituitary releases ADH (anti-diuretic hormone or vasopressin). This helps the retention of sodium and water.

YOUTUBE VIDEO ON THE STRESS RESPONSEhttps://www.youtube.com/watch?v=BIfK0L8xDP0&feature=player_detailpage

In stressful situation, the body switches in its autonomic nervous system and neurobiological processes in an attempt to maintain homeostasis. In the brain, the hypothalamus is connected to the pituitary gland. The hypothalamus stimulated by the sympathetic nervous system releases the hormone CRF. The CRF activates the pituitary gland to release the ACTH hormone; this in turn alerts the adrenal glands. The adrenal glands are located on top of each kidney. The ACTH from the pituitary gland stimulates the adrenal cortex to release cortisol. At the same time, neurons in the hypothalamus signal the medulla to release epinephrine (adrenaline) and norepinephrine. These hormones then push the body into hyper alertness.

Short-Term Stress and Long-Term Chronic Stress Feedback -Short term feedback occurs at the hypothalamus in the anterior pituitary gland. Normally with the activation of the hypothalamus, there is a negative feedback system that decreases further release of cortisol. This increased level of cortisol inhibits the hypothalamus from releasing more CRF and the anterior pituitary from releasing more ACTH. -in the Long-term stress, negative feedback becomes blunted or desensitized and becomes no longer responsive to increased levels cortisol thus enabling the hypothalamus to release more CRF and the anterior pituitary to release ACTH.

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Module 2: Alterations in Hormonal Regulation – Diabetes Diabetes Mellitus Part 1 This module will cover Type 1 and Type 2 Diabetes, as well as briefly addressing gestational diabetes. Learning about the disease of diabetes requires you to have a basic understanding of the anatomy and physiology of the pancreas, liver, and the regular hormonal influences on these organs. I will cover the basics of the anatomy and physiology as it relates to diabetes mellitus. This includes glucose, fat, and protein metabolism, pancreas, hormones of the endocrine pancreas, glucose regulating hormones, the action of insulin on cells. I have included some recommended readings from the School of Nursing’s science textbooks. There is a lot of content in this module. Some of should be a review from previous science courses and some of it will be new or add on to previous learning. The overall aim of this module is to provide the basic science content related to diabetes so that you are then able to apply it into clinical practice. Remember, you will have further opportunity to discuss and apply this content in tutorial sessions and clinical setting. Please note that there is a reference list at the PowerPoint presentation and specific references for each slide are found in the notes section of each slide. Also, the term diabetes will be used interchangeably with diabetes mellitus in this presentation. Diabetes actually means the excessive excretion of urine. Diabetes mellitus refers to the disorder of carbohydrate, fat and protein metabolism with absolute or relative insulin deficiency. Diabetes insipidus will not be covered in this module. Learning Outcomes At the end of this module, you should be able to: - Describe current Canadian trends in the prevalence diabetes mellitus - Describe the etiology of diabetes comparing type 1 & 2 DM and gestational diabetes - Describe glucose, fat and protein metabolism - Identify glucose-regulating hormones and describe their function - Describe the pathophysiology of type 1 and type 2 diabetes mellitus - Link the pathogenesis of DM to the clinical manifestations and evaluation of the disease - Provide scientific rationale for interventions - Provide scientific rationale for patient teaching Complication of diabetes mellitus will be very briefly discussed. The second module on diabetes mellitus will cover in detail, the acute and chronic complications of the disease.

Prevalence of Diabetes According to the National Diabetes Surveillance System in Canada: - In 2006/07 prevalence of diagnosed diabetes increased by 4% from the previous year and 21% from 2002/03 to 2006/07 - Type 2 DM accounts for app. 90% of diabetes cases  Type 1 DM accounts for another 10% with gestational diabetes mellitus and others making up the remaining - 2 million (1 in 16) Canadians are diagnosed with diabetes (2006/07) - > 9 million Canadians live with diabetes or prediabetes  As future nurses, I hope that this statistic and the previous one leads you to recognize the opportunity and need for health education to address prediabetes - Prevalence 6.2% (5.9% females, 6.2% males)  Aged one year and older - Prevalence of diabetes lower in children than adults  The prevalence among children and adolescents is 0.3% while that of the adult is 6.4%.  Among adults, the prevalence increases with age from about 2% of adults in their 30s, peaking at 23% or 1 in 5 adults aged 75-79 years old - Personal costs of premature death and complications  Include reduced quality of life, an increased rate of heart disease, stroke, kidney disease, blindness, amputation, and erectile dysfunction  A staggering 80% of people with diabetes will die as a result of heart disease or stroke  Canadian adults with diabetes are twice as likely to die prematurely  Type 1 diabetic’s life expectancy may be shortened by as much as 15 yrs  Type 2 diabetic’s life expectancy may be shortened by 5-10 yrs - Financial burden  There is tremendous personal societal financial burden to diabetes  A diabetic incurs medical cost that are 2-3 times higher than someone without diabetes o Personal annual medical cost $1000 - $15 000 o Diabetes estimated to cost $16.9 billion/year by 2020 Etiology Type 1 DM Type 1 Diabetes Mellitus is characterized into two types:  Autoimmune Type 1A - accounts for 90-95% of T1D cases  Idiopathic Type 1B

Autoimmune Type 1A - In type 1A there is a autoimmune mediated specific loss of beta cells in the pancreatic islets Langerhans  As a whole, T1D includes cases of diabetes that are primarily the result of beta cells destruction which leads to absolute insulin deficiency and is prone to ketoacidosis. This is believed to be the result of genetic-environment interaction. - Genetic-environment interaction - Genes  There is research underway looking at the genetic susceptibility to T1D  The strongest association and most studied is the inheriting Major histocompatibility complex (MHC) on chromosome 6  In particular, HLA-DR 3 and HLA-DR 4 is associated with an increased risk of Type 1A diabetes, that is 20-40 times higher than that of the general population  It should be noted that some specific human leukocyte antigens are thought to decrease the risk of developing T1D, including HLADR 2  There is also an insulin gene which regulates beta cell replication and function on chromosome 11, which is worth mentioning  There are polymorphisms of multiple genes that have been identified as influencing the risk of Type 1A diabetes that will not be identified in this module  In most cases, there is likely a polygenic inheritance of T1D, meaning that susceptible individuals have more than one genetic polymorphism  Between 10-13% of individuals with newly diagnosed T1D have a first degree relative with T1D  Identifying genes that predispose individuals to diabetes has many advantages but also carries many ethical and legal issues  A discussion of the pros and cons of the genetic testing is beyond the scope of this module, but definitely worth thinking about as it becomes more and more prevalent and relevant to most clinical practice areas o MHC genes on chromosome 6 encode for human leukocyte antigens HLA-DQ and HLA-DR o Chromosome 11- insulin gene regulating beta cell replication & function - Autoantibodies specific to beta cell destruction include: insulin autoantibodies, islet cell autoantibodies, antibodies directed at other islet autoantigens (glutamic acid decarboxylase-GAD & tyrosine phosphatase IA-2) - Environmental factors: drugs & chemicals; nutritional intake; viruses  As mentioned before, environmental factors interact with genes  Certain chemicals such as Alloxan, Streptozotocin, and Vacor as well as certain drugs such as Pentamadine have been associated with T1D

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Nutritional intake of Bovine milk and high levels of Nitrosamines has also been linked to T1D Lastly, viruses have also been linked to T1D 40% of individuals with congenital rubella infection develop T1D later Persistent Cytomegalovirus infection appears relevant in some cases of T1D while mumps and Coxsackievirus’ seem to have small effect on the development of T1D There is a seasonal distribution with more new cases recorded in the Fall and Winter in the Northern Hemisphere This supports the idea that there is a gene environment interaction which causes Type 1A diabetes to manifest There is a small number of adults estimated at approximately 10% classified as having T2D who appear to have immune-mediated destruction of beta cells who actually fall into the category of Type 1A D The term used to describe this sub-population is Latent Autoimmune Disease in Adult (LADA) Otherwise, T1D is diagnosed in childhood for the most part Diagnosis peaks at 12 years of age and is rare before 9 months of age

Etiology Type 1 DM The second subgroup of T1D is Idiopathic Type 1B diabetes. It is sometimes also called Non-Immune Type 1 Diabetes. Idiopathic Type 1B - No evidence of autoimmunity - Accounts for episodic ketoacidosis Etiology Type 2 DM T2D is a heterogeneous condition: - Characterized by hyperglycemia, insulin resistance and relative impairment of insulin secretion (insulin deficiency) - Type 2 diabetes range from predominant insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance - The edeology of type 2 diabetes is thought to involve environment-genetic interaction o The ideology of T2D is thought to involve an environmental genetic interaction o 15-25% of first degree relatives of people with T2D will develop either impaired glucose tolerance or diabetes

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o There is a 2-4 fold increase of T2D associated with a positive family history Genes: genetic defects of beta cell function; genetic defects in insulin synthesis, secretion and action o Variance of genes have been identified that increase the risk of T2D o Many of them fall in the category of genetic defects of beta cell function and genetic defects in insulin synthesis, secretion and action o Others include genes that encode proteins for pancreatic development, amyloid deposition in beta cells, cellular insulin resistance, and impaired regulation of gluconeogenesis Risk factors for T2D include: age, obesity, hypertension, physical inactivity and family history + metabolic syndrome (high risk of developing T2D and associated cardiovascular complications) o Furthermore, there is a high risk of developing T2D and associated cardiovascular complications with metabolic syndrome o Metabolic syndrome will be discussed a little bit later in this module T2D Occurs mostly in adults however there is an increasing prevalence in children as childhood obesity rates climb o Canadian Aboriginal Children are particularly affected o Canadian data regarding the prevalence of T2D is limited US data suggests a 10-30 fold increase in T2D in children over the past 10-15 years

Etiology GDM & Other Gestational Diabetes Mellitus - Any degree of glucose intolerance with onset or first recognition during pregnancy o Pre-gestational diabetes refers to pregnancy in persons with preexisting diabetes - Exact etiology of glucose intolerance in gestational diabetes is unknown. However, a combination of insulin resistance and impaired insulin secretion are most definitely contributing factors o Risk factors for gestational diabetes include: older age, family history, history of glucose intolerance, obesity, membership in certain ethnic or racial groups, history of poor obstetric outcomes, and infant weighing >9 pounds o Diagnosis is made based on the gestational diabetes screen which is a 50g glucose load followed by a plasma gl...