Pathophysiology and Pharmacology Book PDF

25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle Pathophysiology and Pharmacology Book Site: Federation University Moodle Printed by: Dajou Buloba...

25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle Pathophysiology and Pharmacology Book Site: Federation University Moodle Printed by: Dajou Buloba NURBN 2027 SEM2 2024: Nursing Context 7: Date: Friday, 25 October 2024, 1:28 PM Course: Pathophysiology and Pharmacology Applied to Person- Centered Nursing Practice B Combined 001 Book: Pathophysiology and Pharmacology Book Table of contents 1. Introduction 2. Scenario 3. Endocrine Disorders relating to the Thyroid gland 3.1. Hypothyroidism 3.2. Hyperthyroidism 3.3. Thyroid Function Test 4. Endocrine Disorders relating to the Adrenal gland 4.1. Adrenal hormones 4.2. Addison's disease 4.3. Cushing's Syndrome 5. Endocrine Disorders relating to the pituitary gland 5.1. Diabetes Insipidus https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 1/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 1. Introduction  Intended Learning Outcomes After completing this module and with further reading, students should be able to Discuss the negative feedback mechanisms for anti-diuretic hormone (ADH), thyroid hormone (TH) and cortisol. 1. Describe what causes increase secretion of ADH, TH and cortisol, the effect ADH, TH and cortisol to create negative feedback. 2. Discuss the Cause, , Pathophysiology, Progression, Outcome and Treatment of Syndrome of Inappropriate Anti-Diuretic Hormone 3. Discuss the Cause, Pathophysiology, Progression, Outcome and Treatment of Diabetes Insipidous 4. Discuss the Cause, Pathophysiology, Progression, Outcome and Treatment of Hyperthyroidism (specifically Graves Disease) 5. Discuss the Cause, Pathophysiology, Progression, Outcome and Treatment of Hypothyroidism (specifically Hashimoto's disease) 6. Discuss the Cause, Pathophysiology, Progression, Outcome and Treatment of Hypercortisolism (specifically Cushing's Syndrome) 7. Discuss the Cause, Pathophysiology, Progression, Outcome and Treatment of Hypocortisolism (specifically Addisons's Disease) 8. Discuss the Cause,Pathophysiology, Progression, Outcome and Treatment of Diabetes Insipidus Pharmacology Be able to discuss and relate each drug to the disease state it treats by discussing: use/mode of action adverse/side effects ( not nausea or headache), and nursing considerations for each of the following medications: 1. Carbimazole 2. Thyroxine 3. Hydrocortisone 4. Vasopressin  Alignment with Assessment Information in this Week will assist in the successful completion of Assessment Task : Asynchronous Video Presentation and Assessment : Practical Examination  Time Allocation Reading through this book and completing all associated activities is expected to take approximately 4-6 hours and must be done PRIOR to attending any scheduled synchronous class. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 2/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 2. Scenario  Activity - Scenario Complete the scenario to prepare for the pathopthysiology book: https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 3/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 3. Endocrine Disorders relating to the Thyroid gland Overview of the Thyroid Gland The thyroid is a two-lobed, butterfly-shaped gland, measuring approximately 5cm long and 3cm wide, weighing only 30grams. It is located in the lower neck anterior to the trachea. This small organ has a very high blood flow, reflective of the high metabolic activity of the thyroid gland. The thyroid secretes three different hormones (calcitonin, thyroxine [T4] and triiodothyronine [T3]), referred to collectively as thyroid hormones. The thyroid hormone is well known for controlling metabolism, growth, and many other body functions. The thyroid gland, anterior pituitary gland, and hypothalamus comprise a self-regulatory circuit called the hypothalamic-pituitary-thyroid axis. The main hormones produced by the thyroid gland are thyroxine or tetraiodothyronine (T4) and triiodothyronine (T3). Thyrotropin-releasing hormone (TRH) from hypothalamus, thyroid-stimulating hormone (TSH) from the anterior pituitary gland, and T4 work in synchronous harmony to maintain a proper feedback mechanism and homeostasis. Hypothyroidism, caused by an underactive thyroid gland, typically manifests as bradycardia, cold intolerance, constipation, fatigue, and weight gain. In contrast, hyperthyroidism caused by increased thyroid gland function manifests as weight loss, heat intolerance, diarrhea, fine tremor, and muscle weakness.(Shahid et al., 2020). Iodine is an essential trace element absorbed in the small intestine. It is an integral part of T3 and T4. Sources of iodine include iodized table salt, seafood, seaweed, and vegetables. Decreased iodine intake can cause iodine deficiency and decreased thyroid hormone synthesis. Iodine deficiency can cause cretinism, goiter, myxedema coma, and hypothyroidism(Shahid et al., 2020). Thyroid hormone affects virtually every organ system in the body, including the heart, CNS, autonomic nervous system, bone, GI, and metabolism. In general, when the thyroid hormone binds to its intranuclear receptor, it activates the genes for increasing metabolic rate and thermogenesis. Increasing metabolic rate involves increased oxygen and energy consumption. Heart: thyroid hormones have a permissive effect on catecholamines. It increases the expression of beta-receptors to increase heart rate, stroke volume, cardiac output, and contractility. Lungs: thyroid hormones stimulate the respiratory centers and lead to increased oxygenation because of increased perfusion. Skeletal muscles: thyroid hormones cause increased development of type II muscle fibers. These are fast-twitch muscle fibers capable of fast and powerful contractions. Metabolism: thyroid hormone increases the basal metabolic rate. It increases the gene expression of Na+/K+ ATPase in different tissues leading to increased oxygen consumption, respiration rate, and body temperature. Depending on the metabolic status, it can induce lipolysis or lipid synthesis. Thyroid hormones stimulate the metabolism of carbohydrates and anabolism of proteins. Thyroid hormones can also induce catabolism of proteins in high doses. Thyroid hormones do not change the blood glucose level, but they can cause increased glucose reabsorption, gluconeogenesis, glycogen synthesis, and glucose oxidation. Growth during childhood: In children, thyroid hormones act synergistically with growth hormone to stimulate bone growth. It induces chondrocytes, osteoblasts, and osteoclasts. Thyroid hormone also helps with brain maturation by axonal growth and the formation of the myelin sheath. The following picture depicts the location of the thyroid gland and surrounding structures. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 4/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle  Watch Watch this video relating to thyroid hormone production and the negative feedback mechanism controlling the production of thyroid hormones. It depicts the feedback system of the thyroid gland and the role of the thyroid-stimulating hormone. The hypothalamic-pituitary-thyroid axis is where thyroid releasing hormone (TRH) from the hypothalamus stimulates the pituitary gland to secrete thyroid-stimulating hormone (TSH). TSH stimulates the thyroid to produce thyroid hormone (T 3 and T 4 ). High circulating levels of T3 and T4 inhibit further TSH secretion and thyroid hormone production through a negative feedback mechanism Thyroid Gland, Hormones and Thyroid Problems, Animation https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 5/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle this image showcases again, how the production of thyroid hormone is regulated through a feedback mechanism. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 6/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 3.1. Hypothyroidism Hypothyroidism When we are talking about hypothyroidism there are several causative factors - ranging from an autoimmune disorder (Hashimoto's disease ) or primary or thyroidal hypothyroidism which is dysfunction of the thyroid gland itself. Central hypothyroidism is failure of the pituitary gland, hypothalamus or both. Hashimoto's disease is a condition in which the immune system damages the thyroid, reducing its ability to produce thyroid hormones Signs and Symptoms https://gracevillephysio.com.au/blog/physio/physiotherapy-nutrition-hypothyroidism/ The person with hypothyroidism may suffer from extreme fatigue, hair loss, fragile and brittle nails and dry nails are common; numbness and tingling of the fingers may occur. The person's voice may become husky and the patient may complain of being hoarse. Females can have menstrual disturbances such as menorrhagia or amenorrhoea and may experience a loss of libido. In severe cases the person will have a lowered body temperature and pulse rate. The person may begin to gain weight without eating additional food and the skin can become thickened. Hair becomes thin and falls out and face becomes expressionless and often viewed as masklike. the person often complains of being cold even in a warm environment. As the disease progresses though processes slow, speech becomes slow and the tongue enlarges, hands and feet increase in size and deafness may occur. The person may also complain of constipation. Advanced hypothyroidism may produce personality and cognitive changes that are characteristic of dementia. Inadequate ventilation and sleep apnoea may occur in severe cases. Other complications such as pleural effusion and respiratory muscle weakness may also occur. https://gracevillephysio.com.au/blog/physio/physiotherapy-nutrition-hypothyroidism/ Progression The lack of TH causes a decrease in the metabolic rate Outcomes Consider the connection of some of the symptoms below to the effect of too little TH (explain WHY these symptoms occur) Cold intolerance Bradycardia Weight Gain Depression https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 7/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle Fatigue The symptoms above look like the exact opposite of Graves disease....... Column Treatment Replacement of natural L-thyroxine with a synthetic form called L-thyroxine Levothyroxine Regardless of the aetiology for the condition of hypothyroidism, replacement therapy is required and simple with thyroxine (Levothyroxine). This drug comes in oral preparations and is safe, stable, and cheap. The elderly patient initiated on this medication are usually more sensitive to, and experience more adverse reactions, so start low (dose) and go slow (titration). When evaluating and adjusting dosages, clinical response is more important than blood hormone levels, so educating your patient about the side effects and relief of hypothyroidism symptoms is key. General action:thyroid hormone medication characterised by slow onset of action, long duration of action and a half life of 6 to 7 days General use: used in thyroid hormone deficiency(hypothyroidism) and TSH responsive throid tumors General side effects: usually associated with overdosage and consists of nervousness, tremor, sweating, flushing, headache, poor concentration, tachypnoea, tachycardia, palpitations, muscle cramps, vomiting, diarrhea : you guessed it right.. symptoms of hyperthyroidism General interactions: may enhance the clinical effect of warfarin, may reduce the effect of digoxin, may affect the response to oral diabetic agents, caution if given with lithium NSAIDs and corticosteroids General nursing considerations: patient should be warned it may take few weeks for therapy to be effective, needs to be taken on an empty stomach as a single daily dose preferably at the same time, this replacement therapy is life long and may interact with other medications, thyroid function tests should be monitored regularly, patient to report signs and symptoms of overdose. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 8/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle  Watch Watch this video relating to hypothyroidism. It serves as a good summary Hypothyroidism and Hashimoto's Thyroiditis: Visual Explan… Explan… https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 9/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 3.2. Hyperthyroidism Hyperthyroidism Disorders of the thyroid function develop as a result of primary dysfunction or disease of the thyroid gland, or secondarily as a result of pituitary or hypothalamic alterations. Primary throid disorders result in alterations of thyroid hormone (TH) levels with secondary feedback effects on secondary TSH levels. When there is a primary increase in TH level, TSH level will secondarily decrease because of negative feedback and vice versa. When there is excessive TSH production the TH level is elevated secondary to a primary elevation of TSH levels. When the amounts of TH are increased, hyperthyroidism takes place. Remember the hypothalamus release the (TRH) which acts on the anterior pituitary to release the TSH which stimulated the thyroid gland to release TH. The most common type of hyperthyroidism is referred to as Grave's disease, results from the excessive output of thyroid hormones caused by the abnormal stimulation of the thyroid gland by circulating immunoglobulins. It may also be caused by inflammation of the thyroid gland (thyroiditis ) and through the excessive ingestion of thyroid hormone. https://www.pinterest.com.au/pin/265219865530805896/ Radioactive Iodine Radioactive iodine (I-131) or RAI as it shall now be referred to, has been commonly used for the treatment of both benign and malignant thyroid conditions. Iodine is the precursor of thyroxine. The radioactive form of iodine is taken up by iodide transporter of the thyroid the same way as natural iodine and is similarly processed. It destroys the follicular cell, gradually leading to volume reduction and control of the thyrotoxicosis. Signs and Symtoms Often the person with hyperthyroidism presents with nervousness and emotional hyperexcitability, irritability, and apprehension. They will have marked tachycardia on rest as well as on exertion. They perspire freely and do not tolerate heat well causing the skin to be flushed (salmon coloured) and likely to be soft, moist and warm. The patient may present with a fine tremor to the hands. Characteristically they may have exophthalmos (protrusion of one or more of the eyeballs) producing a startled facial expression. They may have an increased appetite and dietary intake although demonstrate a progressive weight loss, they may also have abnormal muscle fatigue and weakness, amenorrhoea and changes in their bowel functioning Treatment https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 10/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle Carbimazole General action It stops thyroid gland from making too much thyroid hormone. For the treatment of hyperthyroidism and thyrotoxicosis. It is also used to prepare patients for thyroidectomy. Carbimazole is a thyroid agent that decreases the uptake and concentration of inorganic iodine by thyroid, it also reduces the formation of di-iodotyrosine and thyroxine. General side effects High temperature, sore throat, mouth sores, toothache or flu-like symptoms – these can be signs of a decreased white cell count. Severe stomach (abdominal) pain – this can be a sign of an inflamed pancreas, jaundice , hypersensitivity reaction.  Watch this video relating to disorders of the thyroid gland namely hyperthyroidism. Hyperthyroidism | Hyperthyroid Endocrine Nursing Sympto… Sympto… General interactions Contraindicated in patients with: A previous history of adverse reactions to it or to any of the excipients in the composition Serious, pre-existing haematological conditions in particular granulocytopenia. Simple goitre. Severe hepatic insufficiency and liver failure Retrosternal goitre and when signs of tracheal compression are present. A history of acute pancreatitis after administration of carbimazole. Should only be administered if hyperthyroidism has been confirmed by laboratory tests. General nursing considerations Assess for contraindications or cautions (e.g. history of allergy, renal stone, pregnancy, etc.) to avoid adverse effects. Assess skin lesions; orientation and affect; liver evaluation; serum calcium, magnesium, and alkaline phosphate levels; and radiographs of bones as appropriate, to determine baseline status before beginning therapy and for any potential adverse effects. Monitor patient response to therapy (lowering of thyroid hormone levels). Monitor for adverse effects (bradycardia, anxiety) Administer at the same time each da  Points to ponder The health history and examination focuses on symptoms that are related to the accelerated or exaggerated metabolism of the patient. some of the nursing interventions that we want to focus on for these patients include: 1. Improving nutritional status - person reports adequate dietary intake and decreased hunger and is able to identify appropriate foods. There is a need to avoid alcohol and other stimulants and there should be a decrease in the episodes of diarrhoea that the person experiences through changes in diet. 2. Enhance coping mechanisms - can explain reasons for irritability and emotional instability; has mechanisms to avoid stressful situations, events and people and has mechanisms that include relaxing, non-stressful activities. 3. Improvement of self-esteem - verbalises feelings about self and illness and can describe and verbalise frustrations and loss of control to others. It is also important that the person can verbalise the reasons for increased appetite. 4. Maintaining normal body temperature - cool, comfortable temperature and changes bedding and clothing as needed. Cool baths and cool or cold fluids may provide relief. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 11/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 5. Monitoring and managing potential complications - cardiac and respiratory functions are assessed by measuring vital signs and cardiac output, ECG monitoring, ABGs and pulse oximetry. O 2 is administered o avoid hypoxia, to improve tissue oxygenation, and to meet the high metabolic demands. IVT may be necessary to maintain BGLs and to replace lost fluids. Anti-thyroid hormones are given to reduce thyroid hormone levels. 6. Education about self-care and continuing care - provide a written plan for the patient to use at home and also to provide appropriate follow-up care if required. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 12/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 3.3. Thyroid Function Test Thyroid Function Test is conducted to identify the status of the thyroid gland. The Thyroid function test includes TRH: Thyrotropin releasing hormone (tripeptide) Secreted by hypothalamus TRH stimulates the release of TSH from the pituitary Inhibited by high levels of T3 and T4 Stimulated by low levels of T3 and T4 TSH: Thyroid stimulating hormone (polypeptide) Released from anterior pituitary Increases production and release of thyroxine (T4 and T3 form the thyroid) Inhibited by high levels of T3 and T4 Stimulated by high levels of TRH and low levels of T3 and T4 T4 : Thyroxine Produced only by the thyroid gland Travels in plasma bound to protein or in free form Converted to T3 (active) and RT3 (inactive) peripherally in blood and tissues T3: Triiodothyronine 85% is produced form converted T4 15% is directly secreted from thyroid 5 times as active as T4 TBG: Thyroid binding globulin Allows carriage of T3 and T4 in blood Inactive when combined with TBG (active component free T3 and T4) Increase: Pregnancy, hepatitis, hypothyroidism Decrease: Thyrotoxicosis, hypoalbuminemia Steroids, phenytoin, NSAID From https://www.google.com/url?sa=i&url=https%3A%2F%2Flitfl.com%2Fthyroid-function-tests%2F&psig=AOvVaw0TNkKco- hX2ec6jfVOU6nd&ust=1682405220108000&source=images&cd=vfe&ved=0CA4QjhxqFwoTCPio0JH2wf4CFQAAAAAdAAAAABAE https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 13/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 4. Endocrine Disorders relating to the Adrenal gland Endocrine Disorders relating to the Adrenal gland The next part of the endocrine system we are going to look at is the adrenal glands. They are located on the superior portion of the kidneys and are made up of two distinct parts, the adrenal cortex, and the adrenal medulla (see image below). The adrenal medulla is part of the autonomic nervous system and releases catecholamines, adrenaline (90%) and noradrenaline when stimulated. The adrenal cortex produces multiple hormones including cortisol (glucocorticoid), aldosterone (mineralocorticoid) and dehydroepiandrosterone [DHEA] (gonadocorticoids). The secretion of hormones from the adrenal cortex is regulated by the hypothalamic-pituitary-adrenal axis (HPA Axis). The hypothalamus secretes corticotrophin-releasing hormone (CRH), which in turn stimulates the pituitary gland to secrete ACTH. ACTH then stimulates the adrenal cortex to secrete glucocorticoid hormone (cortisol). Increased levels of the adrenal hormone then work to inhibit the production or secretion of CRH and ACTH within a negative feedback mechanism. Common disorders associated with alterations in adrenal function are Addison’s disease and Cushing’s syndrome. These diseases have many similarities and differences https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 14/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 15/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 4.1. Adrenal hormones Adrenal hormones In general, the role of the adrenal glands in your body is to release certain hormones directly into the bloodstream. Many of these hormones have to do with how the body responds to stress, and some are vital to existence. Both parts of the adrenal glands — the adrenal cortex and the adrenal medulla — perform distinct and separate functions. Each zone of the adrenal cortex secretes a specific hormone. The key hormones produced by the adrenal cortex include: Cortisol Cortisol is a glucocorticoid hormone produced by the zona fasciculata that plays several important roles in the body. It helps control the body’s use of fats, proteins and carbohydrates; suppresses inflammation; regulates blood pressure; increases blood sugar; and can also decrease bone formation. This hormone also controls the sleep/wake cycle. It is released during times of stress to help your body get an energy boost and better handle an emergency situation. How Adrenal Glands Work to Produce Cortisol Adrenal glands produce hormones in response to signals from the pituitary gland in the brain, which reacts to signaling from the hypothalamus, also located in the brain. This is referred to as the hypothalamic pituitary adrenal axis. As an example, for the adrenal gland to produce cortisol, the following occurs: The hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the pituitary gland to secrete adrenocorticotropin hormone (ACTH). ACTH then stimulates the adrenal glands to make and release cortisol hormones into the blood. Normally, both the hypothalamus and the pituitary gland can sense whether the blood has the appropriate amount of cortisol circulating. If there is too much or too little cortisol, these glands respectively change the amount of CRH and ACTH that gets released. This is referred to as a negative feedback loop. Excess cortisol production can occur from nodules in the adrenal gland or excess production of ACTH from a tumor in the pituitary gland or other source. Aldosterone This mineralocorticoid hormone produced by the zona glomerulosa plays a central role in regulating blood pressure and certain electrolytes (sodium and potassium). Aldosterone sends signals to the kidneys, resulting in the kidneys absorbing more sodium into the bloodstream and releasing potassium into the urine. This means that aldosterone also helps regulate the blood pH by controlling the levels of electrolytes in the blood. DHEA and Androgenic Steroids These hormones produced by the zona reticularis are weak male hormones. They are precursor hormones that are converted in the ovaries into female hormones (estrogens) and in the testes into male hormones (androgens). However, estrogens and androgens are produced in much larger amounts by the ovaries and testes. Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline) The adrenal medulla, the inner part of an adrenal gland, controls hormones that initiate the flight or fight response. The main hormones secreted by the adrenal medulla include epinephrine (adrenaline) and norepinephrine (noradrenaline), which have similar functions. Among other things, these hormones are capable of increasing the heart rate and force of heart contractions, increasing blood flow to the muscles and brain, relaxing airway smooth muscles, and assisting in glucose (sugar) metabolism. They also control the squeezing of the blood vessels (vasoconstriction), helping maintain blood pressure and increasing it in response to stress. Like several other hormones produced by the adrenal glands, epinephrine and norepinephrine are often activated in physically and emotionally stressful situations when your body needs additional resources and energy to endure unusual strai https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 16/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 17/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 4.2. Addison's disease Addison's disease Cortisol is a hormone vital for blood pressure and blood glucose level regulation, immune function and plays a vital role in the body’s anti-inflammatory processes. The impact of cortisol on the body is depicted in the following diagram, now you can imagine if cortisol is in excess or deficient what might occur to the body. Too much Cortisol causes these The following diagram further illustrates in more detail the functions of cortisol during stress, ensure you understand this because it will enable you to gather why alterations in the cortisol levels have such a huge impact on the body. The role of Aldosterone on the body is mainly to regulate sodium and potassium. You recall the renin-angiotensin- aldosterone system which gets stimulated as a result of a low perfusion of blood to the kidneys. Pathophysiology of Addison's Disease Addison's disease, or adrenocortical insufficiency, is where the patient suffers from a lack of cortisol secretion. This is usually (80%) caused by an autoimmune or idiopathic atrophy of the adrenal gland. Addison's disease, also called adrenal insufficiency, is an uncommon disorder that occurs when the body doesn't produce enough cortisol and, often, too little aldosterone. Bilateral adrenal damage or autoimmune disease cause damage to the adrenal cortex causing a decreased level of the adrenal steroid hormones (cortisol and aldosterone ) causing reduced retention of sodium which manifests as hyponatremia and salt cravings; reduced potassium pumped into the kidney tubules causing hyperkalaemia; decreased androgens causing loss of hair and decreased libido; decreased cortisol mediated gluconeogenesis causing hypoglycaemia. Increased renal sodium loss and potassium reabsorption, resulting in decreased intravascular volume, vascular tone, cardiac output, and renal perfusion. This, in turn, lowers arterial blood pressure, which may lead to postural hypotension, compensatory tachycardia, and eventual vascular collapse. Reduced renal perfusion causes water retention, which dilutes the extracellular fluid and causes the cells to leak potassium, leading to hyperkalaemia and metabolic acidosis. Circulatory collapse impairs urinary excretion of waste products, causing elevated levels of blood urea nitrogen and creatinine. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 18/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle Clinical Manifestation Patients with Addison's diseased present with the following signs and symptoms Extreme fatigue Weight loss and decreased appetite Darkening of your skin (hyperpigmentation) Low blood pressure, even fainting Salt craving5 Low blood sugar (hypoglycemia) Nausea, vomiting and diarrhea, leading to dehydration (gastrointestinal symptoms) Abdominal pain, muscle or joint pain or pain in lower back or legs Irritability Depression, mental imbalance or other behavioral symptoms Body hair loss or sexual dysfunction in women High potassium (hyperkalemia) and low sodium (hyponatremia) Other changes include emotional lability, apathy and confusion. If left untreated, an Addisonian crisis can lead to complications such as: · Cardiac arrhythmias from multiple electrolyte abnormalities · Cardiac arrest · Hypotension can lead to orthostatic hypotension and syncope, with progression to a shock state with hypoperfusion to the organs, bradycardia, and myocardial infarction, respiratory failure, ileus, hypoxic brain injury. Hypoglycemia and hypoglycemic coma https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 19/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle Pharmacogic Treatment Hydrocortisone (IV)(Cortef)/ or oral prednisone, to replace cortisol, given on a schedule to mimic the normal 24-hour fluctuation of cortisol levels. (GLUCOCORTICOID) General action: decreases inflammation by stabilising leucocyte lysosomal membranes, suppresses immunity stimulates bone marrow and influences fat, carbohydrates and protein metabolism. General use: Addison's disease and treatment of primary adrenal insufficiency General side effects: insomnia, psychotic behaviour, hypertension, arrhythmia, thromboembolism, peptic ulcer, osteoporosis, cataract, delayed wound healing, increased susceptibility to infection General interactions: increased risk of GI distress with NSAIDs, contraindicated in patients with hypersensitivity to this drug General Nursing considerations:monitor blood glucose level in diabetics, use cautiously in patients with stomach ulcer, monitor weight, electrolytes and blood pressure, low sodium diet to be given with therapy, individulas with diabetes nmay require an adjustment of their insulin dose, caution patient not to discontinue drug abruptly, primary adrenal insufficiency signs and symptoms, long term therapy requires the patient to be placed on low sodium, high potassium diet and taking vitamin D or calcium supplements. Fludrocortisone acetate to replace aldosterone (MINERALOCORTICOID) General action: increases sodium reabsorption and potassium and hydrogen secretion at nephron's distal convoluted tubules General use: addisons disease in combination with hydrocortisone General side effects: sodium and water retention, hypertension, peptic ulcer, hypokalemia, muscle weakness, sweating General interactions: enhanced potassium wasting effect with diuretics such as thiazides, contraindicated in patients with hypersensitivity to this drug General nursing considerations: use cautiously in patients with myocardial infarction, GI ulcer, oral dose to be given with food, rotate IM injection to prevent muscle atrophy, monitor weight, blood pressure, and serum electrolyte s, individuals with diabetes may require insulin dose increase. Patient not to stop the drug abruptly, and to know the signs and symptoms of adrenal insufficiency Points to Ponder 1. Monitoring and managing Addisonian Crisis - usually the manifestations of shock - hypotension, rapid, weak pulse, rapid respiratory rate, pallor and extreme weakness 2. Restoring fluid balance - assessing skin turgor, mucous membranes and weight. Patients also need to self-report any increases in thirst. 3. Improving activity tolerance - avoid unnecessary activity and stress that may precipitate another Addisonian crisis 4. Educating patients about self-care - provide written explicit instructions about management of medications and modifications during times of stress or illness. Encourage the use of medic-alert bracelets and to carry information at all times about their condition. Looking out for symptoms of high and low hormone levels. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 20/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle https://cdnrmi-19948.kxcdn.com/cdn/ff/NvTO04K4Yzb9CRB855_8FF2uCw5pbosr-cuMGgBHvR4/1613992210/public/Disease-2021- 02/Addisons%20disease.jpg https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 21/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 4.3. Cushing's Syndrome Cushing's Syndrome Cushing’s syndrome, on the other hand, results from an excessive amount of cortisol secretion. This excess cortisol secretion is often from a tumour which secretes cortisol, or excessive ACTH production which in turn increase cortisol secretion. In almost 80% of cases, this tumour lies within the pituitary gland. The remaining 20% of these tumours are within the adrenal cortex or other non-associated organs such as the thyroid, pancreas or thymus. The other alternative for excess cortisol production is from people receiving prolonged or high dose treatments with glucocorticoid drugs. Clinical Manifestations https://www.pinterest.com.au/pin/37576978118936433/ The cause of the excessive amount of cortisol will dictate the treatment. In individuals with primary adrenal hypertrophy, the management is an adrenalectomy. There may be a need for replacement therapy for these patients, depending on if one or both adrenal glands are removed. However, if the cause is from the administration of corticosteroids, the dosage will be looked at with the intention to reduce or cease the administration Points to Ponder Goals of therapy include 1. Decreased risk of injury - free of fracture and soft tissue injuries and free of ecchymotic areas 2. Decreased risk of infection - avoid exposure to others with infections and nurse frequently should assess for infection (temperature elevation, redness and pain) 3. Increase participation in self-care activities - plan activities and exercises to allow alternating periods of rest and activity. Report improved wellbeing and is free from the complications that are associated with immobility. 4. Attain/maintain skin integrity - the person has intact skin without evidence of breakdown or infection. Exhibits decreased oedema in extremities and trunk and changes position frequently and inspects bony prominences daily. 5. Achieve a positive body image - verbalise feelings about changes in appearance, sexual functioning and activity levels. Person understands that changes in the person's physical appearance are due to excessive corticosteroids. 6. Person demonstrates improved mental functioning https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 22/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 7. Absence of complications - normal vital signs and weight and free from Addisonian crisis. Identifies signs and symptoms of adrenocortical hypofunction that should be reported and measure to take in case of severe illness and stress. Person identifies strategies to minimise complications of Cushing's syndrome and complies well with recommendations for follow- up appointments and health screening.  Watch this video appertaining to Cushing's syndrome Cushing Syndrome, Animation https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 23/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 5. Endocrine Disorders relating to the pituitary gland Endocrine Disorders relating to the pituitary gland Now we will be focusing on another gland, the pituitary gland. The pituitary gland is a small pea-sized gland that plays a major role in regulating vital body functions and general wellbeing. This gland is housed within a bony structure (sella turcica) at the base of the brain. The sella turcica protects the pituitary but allows very little room for expansion. The pituitary is referred to as the body's 'master gland' because it controls the activity of most other hormone-secreting glands. Refer to the image below to review the hormones released from the posterior and anterior part of the pituitary gland. For example, from the anterior pituitary, adrenocorticotropic hormone is releases which acts on the adrenals of the kidney to release the adrenal hormones. The posterior pituitary gland only secretes a few hormones under neural stimulation by the hypothalamus. One of which is anti-diuretic Hormone (ADH). The condition Diabetes Insipidus is connected to the function of this hormone. Remember that there is a negative feedback loop. Negative mechanism for ADH: https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 24/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle ❮ Scenario template https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 25/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle 5.1. Diabetes Insipidus The major adverse effect of desmopressin for which to monitor is hyponatremia Causes Diabetes insipidus is caused by problems with a chemical called vasopressin (AVP), which is also known as antidiuretic hormone (ADH). AVP is produced by the hypothalamus and stored in the pituitary gland until needed. The hypothalamus is an area of the brain that controls mood and appetite. The pituitary gland is located below your brain, behind the bridge of your nose. AVP regulates the level of water in your body by controlling the amount of urine your kidneys produce. When the level of water in your body decreases, your pituitary gland releases AVP to conserve water and stop the production of urine. In diabetes insipidus, AVP fails to properly regulate your body's level of water, and allows too much urine to be produced and passed from your body. There are 2 main types of diabetes insipidus: neurogenic diabetes insipidus – where the body does not produce enough AVP, so excessive amounts of water are lost in large amounts of urine nephrogenic diabetes insipidus – where AVP is produced at the right levels, but, for a variety of reasons, the kidneys do not respond to it in the normal way Progression (effect) Water is lost at a very fast rate (remember water and not salt). Up to 12L a day can be passed! This can lead to dehydration. However, the largest issue is hypernatremia. Look up hypernatremia (pg 152-153 of your textbook) note some of the more fatal symptoms in this image and the treatment for this condition Outcome If left untreated, coma and death. Treatment The primary treatment of DI is by using synthetic vasopressin (more on this in the pharmacology section). However, there may be a need to correct electrolytes first using IV therapy (what kind of fluid would correct this? hypertonic or hypotonic?) https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 26/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle Source: Craft (2019) Understanding pathophysiology Desmopressin General action Desmopressin is a selective vasopressin V2 receptor agonist present throughout the collecting ducts and distal convoluted tubules of the kidneys General side effects. The major adverse effect of desmopressin for which to monitor is hyponatremia. In certain instances, the hyponatremia caused by this drug can precipitate seizures. The minor adverse effects that may affect individual patients are headaches, tachycardia, and facial flushing. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 27/28 25/10/2024, 13:28 Pathophysiology and Pharmacology Book | Moodle General contraindications Hyponatremia is an absolute contraindication to the administration of desmopressin. Desmopressin acts primarily in the nephron; this drug is contraindicated in patients with renal impairment. Also, patients suffering from thrombocytopenic purpura should not receive desmopressin, as it can precipitate a thrombotic event General Nursing considerations Patients receiving desmopressin need monitoring for the occurrence of hyponatremia. Symptoms of hyponatremia include nausea, confusion, or altered mental status. As patients age, they should also be continually monitored for declining renal function, as the therapeutic index and clearance of the drug will change according to the renal function.  Watch this video relating to diabetes insipidus. Understanding Diabetes Insipidus https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654087 28/28