Pathophysiology and Pharmacology Book PDF

21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle Pathophysiology and Pharmacology Book Site: Federation University Moodle Printed by: Dajou Buloba...

21/10/2024, 18:31 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: Monday, 21 October 2024, 6:31 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. Diabetes Mellitus 3.1. Diabetes Mellitus 3.2. Treatment of Diabetes: Insulin 3.3. Exogenous Insulin 3.4. Treatment of Diabetes Mellitus: Oral Hypoglycemic Agents 3.5. Chronic Complications of Diabetes Mellitus 3.6. Acute Complications: Hypo and Hyperglycemia 3.7. Acute Complications of Diabetes Mellitus 3.8. Acute Complications of Diabetes Mellitus 4. Patient Education https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 1/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 1. Introduction  Intended Learning Outcomes Upon completion of this week's learning, and with further reading from your prescribed text/extra learning resources you will be expected to: 1. Discuss the Cause, Progression, Outcome and Treatment of Type 1 Diabetes Mellitus: - The effect of autoimmune dysfunction on the pancreas, the result of beta islet cell destruction, clinical manifestations, the medical treatment and chronic complications 2. Discuss the Cause, Progression, Outcome and Treatment of Type 2 Diabetes Mellitus: - Causes of T2DM, effect of insulin resistance and pancreas insufficiency on glucose utilisation, clinical manifestations of T2DM the medical treatment and chronic complications (Complications of Diabetes: Micro and Macrovascular) 3. Discuss the cause, progression, outcome and treatment of the acute complications Diabetic Ketoacidosis and HHNS Pharmacology 1. Discuss the use insulin in terms of - types: examples, onset of action, peak time; administration routes, nursing considerations. 2. Discuss the use of , side effects, contraindications and nursing consideration of Biguanides 3. Discuss the use of, side effects , contraindications and nursing consideration of Sulphonylureas 4. Discuss the use of, side effects, contraindications and nursing consideration of Thiazolidinediones (glitazones) 5. Discuss the use of, side effect, contraindicatios and nursing consideration of Dipeptidyl peptidase IV (DPP-4)  Alignment with Assessment Information in this Week will assist in the successful completion of Assessment Task: Asynchronous Video Presentation and Assessment : Practical Exam  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=7654074 2/23 21/10/2024, 18:31 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=7654074 3/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3. Diabetes Mellitus Diabetes Type I Type 1 diabetes is an autoimmune condition where the body’s own immune system is activated to destroy the beta cells in the pancreas which produce insulini. We do not know what causes this autoimmune reaction however environmental factors are thought to set off the process. Type 1 diabetes is not linked to modifiable lifestyle factors. Currently there is no cure and it is lifelong. Type 1 diabetes: Occurs when the pancreas does not produce insulin Represents around 10 per cent of all cases of diabetes and is one of the most common chronic childhood conditions In children, onset is usually abrupt and the symptoms obvious In adults, onset is slower Symptoms can include excessive thirst and urination, unexplained weight loss, weakness and fatigue and blurred vision Is managed with insulin injections several times a day or the use of an insulin pump In type 1 diabetes, the pancreas, stops making insulin because the beta cells that make the insulin have been destroyed by the body’s own immune system. Without insulin, glucose (a type of sugar) cannot enter the body’s cells where it is usually turned into energy. Signs and Symtoms Being excessively thirsty (Polydipsia) Passing more urine (Polyurea) Feeling tired and lethargic Always feeling hungry (Polyphagia) Having cuts that heal slowly Itching, skin infections Blurred vision Unexplained weight loss Untreated type 1 diabetes results in diabetic ketoacidosis (DKA), a medical emergency. Management and Care Type 1 diabetes is managed with insulin injections several times a day or the use of an insulin pump. Insulin can’t be taken as a tablet as it would be digested down to its building blocks, amino acids, by the body’s normal digestive process. Glucose levels can be measured using a blood glucose monitor or a continuous glucose monitor which measures glucose in the body’s interstitial fluid.  Engage From the information in the resources and your own research, develop your own table listing the characteristics (age, gender, ethnic groups commonly affected, obesity) and etiology (causative factors) for Type 1 Diabetes in Australia. Post your table on the discussion forum and compare yours to others  Watch this video explaining the pathophysiology of Type 1 and 2 Diabetes https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 4/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle Diabetes Type 1 and Type 2, Animation. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 5/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.1. Diabetes Mellitus Diabetes Mellitus Type II Type 2 diabetes is a condition in which the body becomes resistant to the normal effects of insulin and gradually loses the capacity to produce enough insulin in the pancreas. The condition has strong genetic and family-related (non-modifiable) risk factors and is also often associated with modifiable lifestyle risk factors. We do not know the exact genetic causes of type 2 diabetes. People may be able to significantly slow or even stop the progression of the condition through changes to diet and increasing the amount of physical activity they do. Type 2 diabetes: Is diagnosed when blood glucose levels are high due to insulin produced by the pancreas not working effectively and/or the cells of the body do not respond to insulin effectively (known as insulin resistance), over time the condition progresses and the pancreas does not produce enough insulin (reduced insulin production) Represents 85–90 percent of all cases of diabetes Usually develops in adults over the age of 45 years but is increasingly occurring in younger age groups including children, adolescents, and young adults Is more likely in people with a family history of type 2 diabetes or from particular ethnic backgrounds For some, the first sign may be a complication of diabetes such as a heart attack, vision problems or a wound that does not heal well Is managed with a combination of regular exercise, dietary regulation, and weight reduction. As type 2 diabetes can be progressive, many people will need oral medications and/or insulin injections in addition to lifestyle changes over time Type 2 diabetes develops over a long period of time (years). During this period of time insulin resistance starts, this is where the insulin is increasingly ineffective at managing the blood glucose levels. As a result of this insulin resistance, the pancreas responds by producing greater and greater amounts of insulin, to try and achieve some degree of management of the blood glucose levels. Key Concept: As insulin overproduction occurs over a very long period of time, the insulin- producing cells in the pancreas wear themselves out, so that by the time someone is diagnosed  with type 2 diabetes, they have lost 50 – 70% of their insulin-producing cells. This means type 2 diabetes is a combination of ineffective insulin and not enough insulin. Lifestyle changes may be able to slow this process in some people. Signs and Symptoms Many people with type 2 diabetes have no symptoms. As type 2 diabetes is commonly (but not always) diagnosed at a later age, sometimes signs are dismissed as a part of ‘getting older’. In some cases, by the time type 2 diabetes is diagnosed, the long-term complications of diabetes may already be present. Symptoms are similar to type I ie polyphagia, polydypsia, polyurea, skin infections, lethargy, drowsiness, poor wound healing and mood swings Management and Treatment While there is currently no cure for type 2 diabetes, the condition can be managed through lifestyle modifications and medication. Effectively managing diabetes is the best way to prevent diabetes-related complications. Eating a healthy diet helps to keep blood glucose levels within target range, which reduces the risk of developing diabetes- related complications. More whole, unprocessed foods and less processed or packaged foods Regular meals spread evenly throughout the day Diet lower in fat, particularly saturated fat Between-meal snacks to avoid hypoglycemia Exercise can help: Insulin to work better, which will improve diabetes management Reduce insulin resistance and reduce blood glucose levels Improve joint and muscle movement, and strengthen bones Maintain a healthy weight Note: BGL should be monitored before and after exercise https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 6/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle Oral hypoglycemic agents if healthy eating and exercise are not suffice  Watch this video relating to Diabetes Mellitus II pathophysiology Diabetes Type II Pathophysiology https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 7/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.2. Treatment of Diabetes: Insulin Treatment of Diabetes: Insulin We need to have a quick review of what insulin is and why it is essential to life. Insulin is defined as the body’s main fuel storage hormone and is secreted in response to raised levels of glucose in the blood. Its purpose is to ensure that the tissues have sufficient chemical substrates for energy, storage, anabolism, and repair. Geez, that sounds pretty important and we can appreciate its value to human existence. Now if you are familiar with how insulin works then you can skip ahead to the next page. If you need more learning on the discrete mechanisms, please read on. Insulin is an incredibly important to understand well. Insulin is released into circulation in two manners: a low basal release via the capillaries into the portal circulation to the liver and bolus release in response to stimuli (glucose absorbed from oral intake) via an excitation-secretion coupling process. Conversely, a fall in glucose or fasting directly inhibits insulin secretion. This leads us to the other primary hormone of the pancreas, glucagon, which increased release into the bloodstream to facilitate the breakdown of liver glycogen to raise and restore blood glucose levels. Think of insulin as the key to unlock the cell so glucose can enter. No key, door closed, no energy. In the diagram below, the green arrows indicate what happens when blood glucose is low, while the red arrows show what happens when blood glucose is high. Note that the liver, pancreas, glucose and insulin are all vital in maintaining the blood glucose levels. As you know, insulin is released in response to ingestion of carbohydrates by the beta cells of the pancreas. As a result, excess glucose not needed by the body will be stored in the liver and muscles in the form of glycogen or used to form fat by the adipose tissues. In response to low carbohydrate intake, the body senses a decreased level of glucose in the blood, hence glucagon will be released by the alpha cells of the pancreas to convert stored glycogen in the liver and muscled back into glucose. To recap Insulin is: an anabolic hormone, which means it builds molecules. It is important in building cell proteins, lipids and nucleic acids. produced by the pancreatic beta cells. secreted in response to: high levels of glucose, amino acids and fatty acids in the blood. How does insulin work? Insulin binds with and enters the cell, initiating a chain of events that allows the glucose transport mechanism to travel from inside the cell to the cell border, allowing glucose into the cells. If the cell is not ‘sensitive’ to insulin binding, glucose entry into cells is impaired. What inhibits the function of insulin? Low glucose levels, negative feedback from high insulin levels and sympathetic nervous system stimulation of alpha cells. Major effect of insulin It reduces the blood glucose level by increasing uptake of glucose by the cells Regulation: chemical, hormones, nervous system The brain, nerves and kidneys do not require insulin for glucose entry into cells. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 8/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle  Watch this video identifying how insulin is regulated in the body Insulin, glucagon, & glycogen regulation. (Made simple with… with… https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 9/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.3. Exogenous Insulin Exogenous Insulin Before we discuss exogenous insulin, the following image summarises how type I diabetes mellitus differs from type II. While in a normal individual the insulin hormone works on its receptors to convert glucose into glycogen, in type I the pancreas fails to produce insulin and in type II the receptors fail to respond to insulin appropriately. Insulin Administrator Now that you have an appreciation for what insulin is and how it works, we’re going to move into discussing the characteristics of exogenous insulin, including the onset of action, peak effect and duration of action. This can be seen in the image below where the curves indicate approximate times of onset, peak and duration of hypoglycemic activity of the main types of insulin formulations. It is important to know the Onset, Peak and Duration of each type of insulin inorder to understand its effectiveness. You will notice that each pharmaceutical company name the insulin a different name, familiarise yourself with the names, but make sure you understand how each type works. The following image shows you the different types of insulin available, how the insulin appears, the different brand names and difference in activity ( onset/peak/ duration). You will find in clinical practice that many patients with diabetes are on more than one preparation or maybe even a combination like Humulin 30/70. We know that all persons with Type 1 diabetes will need to administer exogenous insulin as they do not produce insulin. We know that many persons with Type II diabetes may also be taking exogenous insulin as they typically have insulin resistance (the key fits but doesn’t unlock the door). We also know that we need to have a good idea of the characteristics of all the insulin preparations in order to administer them safely. Understanding the mechanism of action of insulin, we would automatically know that by unlocking the cell to allow glucose to leave the bloodstream and enter the cell, an adverse effect of insulin would be hypoglycaemia and this is also an absolute contraindication as well. There are many drugs that affect the blood glucose level and thus will interact with insulin and impair diabetes control. Medications that induce hyperglycemia are corticosteroids, opioids, beta agonists, adrenaline and loop diuretics. Medications that induce hypoglycemia are beta blockers and NSAIDS. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 10/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle Patient Education The next image enlists the teaching you need to provide to your patients who have been newly diagnosed with diabetes. Patient education should be directed at correct administration, checking the blood glucose level prior to injection, drawing the medication and time of administration. Further, you should teach the patient the signs and symptoms of hypoglycemia, complications of diabetes and proper storage of insulin. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 11/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.4. Treatment of Diabetes Mellitus: Oral Hypoglycemic Agents Treatment of Diabetes Mellitus: Oral Hypoglycemic Agents Moving on to the oral hypoglycaemic agents (OHAs), there are several classifications of medications within this area and these agents are used only in the treatment of type 2 diabetes. As depicted in the image below, OHAs act on different pathways within the endocrine system to lower blood glucose levels. These can be summarised into the following: Simulate further insulin release Lower insulin resistance Sensitise cells to the actions of insulin Reduce glucose load Enhance functions of incretins Alter absorption of carbohydrates. 1. Biguanides: Insulin sensitisers (Metformin) This drug has been around for ages and is the only OHA that reduces mortality; so naturally, it’s the first line treatment option General Action: Decreases hepatic glucose production and intestinal absorption of glucose and improves insulin sensitivity , has an antiketogenic activity (preventing or suppressing the development of ketones (ketone bodies) and thus preventing development of ketosis) General use: adjunct to diet to lower blood glucose level in individuals with type 2 diabetes mellitus General side effects: diarrhea, nausea , vomiting, abdominal pain, lactic acidosis, unpleasent or metallic taste General interactions: beta blockers possible masked signs of hypoglycemia, calcium channel blockers, corticosteroids, oral contraceptives , thiazide diuretics : possible hyperglycemia, interacts with contrast dye causing acute renal failure, interacts with alcohol causing potentiated drugs effect General nursing considerations: monitor blood glucose level, it is excreted in the urine unchanged, which means one needs to be aware of renal function prior to initiating therapy. This agent is contraindicated in patients that are at risk of developing lactic acidoses, like liver disease, the elderly and those taking alcohol or drugs that raise metformin levels. This explains why in the clinical setting, you’ll see this agent held when a patient is undergoing a procedure that involves contrast dye so that the patient avoids developing lactic acidosis.renal function tests should be evaluated prior to commencing therapy and consistently after, should be administered with meals 2. Thiazolidinediones ‘glitazones’( pioglitazone, rosiglitazone) General actions: lowers blood glucose level by decreasing insulin resistance improves the sensitivity of insulin in muscle and adipose tissue General use: adjunct to diet and exercise to improve glycemic control in individuls with type 2 diabetes General side effects:headache, oedema, sinusitis, hypoglycemia with combination therapy, General interactions: possible reduced plasma levels of oral contraceptives General Nursing considerations:advise women taking the drug and oral contraceptive s to consider additional birth control measures, contraindicated in patients with hypersensitivity to drug , liver disease and diabetic ketoacidosis. Use cautiously in patients with oedema and heart failure, monitor liver function tests before and through the therapy, monitor blood glucose level regularly, instruct patient to adhere to dietary instructions , make sure the patient is aware of the signs and symptoms of hpo/ hyperglycemia 3. Sulfonylureas(glibenclamide, glipizide, and gliclazide General action:stimulate insulin release from functioning pancreatic cells. Improve the sensitivity of beta cells to glucose stimulus and reduce basal glucose production by the liver https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 12/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle General use: type 2 diabetes unresponsive to diet alone and in whom other antidiabetic agents have been ineffective General side effects:hypoglycemia, anorexia, nausea, vomiting, blurred vision, elevated liver enzymes General interactions: hypoglycemic action is enhanced with ACE inhibitors, alcohol, beta blockers, other oral antidiabetic agents, NSAIDS. Hypoglycemic action is reduced with corticosteroids and calcium channel blockers, frusemide, may either increase or decrease the effects of warfarin General Nursing considerations: monitor blood sugar level and liver function tests before and during therapy, patient should be instructed that these are not an oral form of insulin but may increase circulating insulin, avoid strenous exercise and alcohol consumption with therapy, contraindicated in patients with allergy to sulfur. 4. Dipeptidyl Peptidase 4 inhibitors (DDI): linagliptin, saxagliptin, sitagliptin (has gliptin as a suffix) General action: enhances the level of incretin hormones which are responsible for regulation of glucose homeostasis, improves beta cells responsiveness to glucose and stimulates insulin synthesis and release, reduces glucagon secretion from the alpha cells of the pancreas hence decreasing liver glucose General use: type 2 diabetes inadequately controlled by diet General side effects: headache, pancreatitis, hypoglycemia, hypersensitivity, bronchial hyperactivity General interactions:Not recommended during pregnancy, minimal interaction with other drugs General nursing considerations: make sure patient is aware of the increased risk of hypoglycemia if taken with other antidiabetic agents, not recommended in patients with severe liver impairment. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 13/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.5. Chronic Complications of Diabetes Mellitus Now we will explore the chronic (long term) complications of Diabetes Mellitus. Generally, these complications can be either microvascular or macrovascular. Microvascular Complications Microvascular complications affect the smaller blood vessels, such as in the eyes (leading to retinopathy), kidneys (leading to nephropathy), and neurons (leading to neuropathy). Individuals with poorly managed blood glucose levels may suffer from one or more of these complications in advanced stages of the disease. Thus, besides monitoring the health of eyes and kidneys, diabetics also require foot care. S tudies have shown that aggressive management of blood glucose levels (i.e., keeping blood glucose levels within a narrow range) can avoid, or at least delay, the onset of these complications. Therefore, monitoring and management of blood glucose levels is of critical importance in maintaining metabolic balance and avoiding microvascular complications. With regards to how this occurs, it is thought that metabolic injuries resulting from prolonged exposure to high blood sugar cause altered blood flow and changes in endothelial permeability, extravascular protein deposition and coagulation resulting in organ dysfunction. 1. Diabetic Retinopathy occurs following hyperglycaemia-mediated damage within the retinal microvasculature. This damage causes basement membrane thickening, increased capillary permeability and the formation of microaneurysms. These changes cause intravascular coagulation, resulting in retinal ischaemia which drives the formation of new vessels within the retina (neovascularisation). These new vessels are fragile and may rupture causing retinal bleeds. Furthermore, the lack of lymphatic drainage within the retina causes fluid accumulation in the presence of hyperglycaemia resulting in macular oedema. 2. Nephropathy Diabetic nephropathy arises from hyperglycaemia and hypertension driving glomerular damage. The increased glomerular filtration pressures result in albuminuria, a driver for ongoing renal damage and the first step towards developing overt proteinuria (loss of protein in the urine). 3. Neuropathy Diabetic neuropathy refers to various neurological disorders associated with diabetes. The main sequel of neuropathy is foot deformity, ulceration. The combination of neuropathy, arteriopathy and infection are the driving factors behind most diabetic foot amputations. Macrovascular Complications https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 14/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle Macrovascular complications affect the circulatory system and include ischemic heart disease, peripheral vascular disease and cerebrovascular disease.The causes of these complications stem from narrowing of blood vessels due to glycation, inflammation, lipid deposition and other factors. 1. Cardiovascular disorders in diabetes include premature atherosclerosis, manifest as myocardial infarction and stroke as well as impaired cardiac function, predominantly diastolic dysfunction. The endothelium ( the thin membrane lining the inside of the heart and blood vessels is crucial for maintenance of vascular homeostasis, ensuring that a balance remains between vasoactive factors controlling its permeability, adhesiveness, and integrity , but this balance appears compromised by diabetes. Atherosclerotic changes cause he formation of a complex atherosclerotic plaque, which may occlude the blood vessel at the site of formation such as in the coronary or femoral circulation or become an embolus occluding blood vessels at distant sites. Obstruction of blood vessel circulation from a clot in the brain causes stroke 2. Peripheral vascular disease Peripheral vascular disease is the reduced circulation of blood to a body part, other than the brain or heart, due to a narrowed or blocked blood vessel. Reduced blood supply to the extremities especially the feet combined with the microvascular complication of neuropathy will result in poor wound healing in the feet and a heightened risk to acquire foot damage due to reduced sensation in the area. This explains why diabetic patients may require leg amputation. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 15/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.6. Acute Complications: Hypo and Hyperglycemia Acute Complications: Hypo and Hyperglycemia Hyperglycemia Hyperglycemia denotes fasting blood glucose level above 6 mmol/l or non-fasting blood glucose level above 8mmol/l. Several factors can contribute to hyperglycemia including food choices (processed and high sugar), low physical activity, illness, non-diabetes medications (such as corticosteroids, skipping or not taking enough glucose-lowering medication or insulin. In the long term, persistent high blood glucose levels causes damage to blood vessels leading to complications that affect the nerves, eyes, kidneys and heart. Management is aimed at monitoring BGL, medications (insulin/oral antidiabetic agents), hydration, managing the cause of hyperglycemia and monitoring for signs and symptoms of complications such as DKA and HHNS. Check this image regarding the signs and symptoms of hyperglycemia. Note that Hyperglycaemia may not cause symptoms until blood glucose levels are consistently over 10mmol/L. Hypoglycemia Hypoglycemia denotes a blood glucose level less than 4mmol/l. There are many reasons why you may have low blood sugar, including: Taking too much insulin Not eating enough carbs for how much insulin you take. Timing of when you take your insulin. Prolonged and strenuous physical activity. Drinking alcohol. How much fat, protein, and fiber are in the meal. If blood glucose stays low for too long, starving the brain of glucose, it may lead to seizures, coma, and death. The signs and symptoms and management of hypoglycemia are showcased in the image below https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 16/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 17/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 18/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.7. Acute Complications of Diabetes Mellitus On this page and next, we direct our focus on the acute complications of diabetes mellitus; particularly diabetic ketoacidosis and hyperglycemic, hyperosmolar nonketotic syndromer (HHNS) Diabetic Ketoacidosis Insulin deficiency, increased insulin counter-regulatory hormones (cortisol, glucagon, growth hormone, and catecholamines) and peripheral insulin resistance lead to hyperglycemia, dehydration, ketosis, and electrolyte imbalance which underlie the pathophysiology of DKA. Despite high blood glucose levels, the body cells (muscle and lipid cells) may be starved for glucose due to absence or improper function of insulin.Cells may also starve for glucose if the amount of food intake is low (such as during illness) or if the dosage of insulin is too high. Under these conditions cells start using fats as a source of energy. Due to increased lipolysis (break down of fat) and decreased lipogenesis (formation of fat ), abundant free fatty acids are converted to ketone bodies by Liver cells. When the glucose levels are low, brain cells can use ketone bodies, but not free fatty acids, for energy. High concentrations of ketones can make the urine acidic and cause fruity-smelling breath. If not managed, this condition can progress to coma (prolonged unconsciousness) and even death. Study the image below, note how DKA results from a triad of ketogenesis(formation of ketones) gluconeogenesis (formation of glucose from sources other than glucose) and glycogenolysis (breakdown of glycogen to make more glucose). Note how the signs and symptoms include fruity breath, decreased level of consciousness, tachypnea, tachycardia, polydipsia and dehydration due to polyurea. Also note that this condition occurs for TYPE I Diabetes due to no insulin. Management is directed to achieve the following goals Airway, breathing circulation DKA patients need to have their airway, breathing and circulation assessed immediately. A patient that is in severe DKA may be unconscious with an unprotected airway and compromised breathing. They are also at risk of circulatory collapse from severe dehydration, with a loss of 6 – 10 litres of fluid volume on presentation to the hospital. Due to the extremely acidotic environment and electrolyte derangements, these patients are also at high risk of experiencing a cardiac arrest Fluid resuscitation Due to the increased blood glucose levels and increased ketones, there is an increase in intravascular osmolality. This leads to a large fluid depletion due to the osmotic diuresis which fluid resuscitation rectifies. Potassium replacement potassium needs to be closely monitored and replaced as required (usually with an intravenous potassium infusion) Insulin replacement while monitoring for signs of hypoglycemia Acidosis management Acidosis is only actively managed with replacing bicarbonate if pH < 7.0, Monitor patient for complications can include dehydration, hypovolemia, hypotension, electrolyte abnormalities, cardiac arrhythmias, cardiac arrest and cerebral oedema. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 19/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 20/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 3.8. Acute Complications of Diabetes Mellitus Acute Complications of Diabetes Mellitus Hyperglycemic Hyperosmolar Nonketotic Syndrome Hyperosmolar Hyperglycemic Syndrome (HHNS) is a clinical condition that arises from a complication of diabetes mellitus Type 2. As a consequence of deficiency of the key hormone insulin, there is a decrease in glucose utilization by the peripheral tissue causing hyperglycemia. The peripheral tissues enter a state of “starvation.”The release of counterregulatory hormones like glucagon, growth hormone, cortisol, and catecholamines stimulates gluconeogenesis (new glucose formation) ang glycogenolysis (breakdown of glycogen to form glucose). HHNS is therefore characterised by 1) severe hyperglycaemia (>30 mmol/L) higher than that in DKA , which leads to an osmotic diuresis. This leads to 2) profound dehydration, hypovolaemia and 3) plasma hyperosmolality (>320 mosm/kg) with hypernatraemia. The hypernatraemia can cause an altered mental state and, in extreme cases, coma. In HHNS, however, because insulin is still being produced by the beta cells in the pancreas, the generation of ketone bodies is minimal. Insulin inhibits ketogenesis so symptoms like ketone breath are not present. Management Resuscitation priorities should be made: securing a safe airway; ensuring adequate ventilation; followed by correction of fluid losses. Rehydration while maintaining electrolyte homeostasis should be the first focus of treatment.. Fluid replacement should take into consideration comorbidities such as cardiac and renal failure. Rapid reduction in serum sodium should be avoided due to the risk of cerebral oedema, hence normal saline is the preferred rehydration fluid. The goals of treatment are to gradually correct the osmolality and electrolyte disturbances Replace potassium depletion is present in HHNS despite normal plasma levels. Reverse Hyperglycaemia: An over-rapid correction of blood glucose prior to rehydration can precipitate cardiovascular collapse. Blood glucose levels should be kept at 10–15 mmol/L for the first 24 hours, and IV glucose will be commenced if blood glucose falls too quickly. Following resuscitation and return to normal fluid balance, subcutaneous insulin should be commenced. 11 Treat any underlying disease process such as infection which may have contributed to the hyperglycaemic crisis. Venous thromboembolism risk: The dehydration effects of HHS predispose patients to arterial and venous thromboembolism, so anticoagulation with low molecular weight heparin is recommended. Foot care: Patients with HHS who are obtunded or uncooperative are at high risk for foot damage, so heel protection and regular foot checks are important Disposition: Ensure expeditious transfer of high-risk patients to a centre with a high dependency unit (HDU). Features of concern include plasma osmolality >350 mosm/kg, signs of shock, reduced GCS, sodium >160 mmol/L or renal failure.  Key Concept High insulin levels, a feature of the insulin resistance found in T2DM, supresses lipolysis and ketogenesis. Therefore, acidosis is not a defining feature of HHS https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 21/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 22/23 21/10/2024, 18:31 Pathophysiology and Pharmacology Book | Moodle 4. Patient Education Patient Education In educating the patient with diabetes , it is crucial you explain the complications, prevention,treatment, signs and symptoms of hyper and hypoglycemia. You need to discuss the importance of healthy diet, quitting smoking, regular exercise and foot care. The image above is a general guide on the topics to be discussed. https://moodle.federation.edu.au/mod/book/tool/print/index.php?id=7654074 23/23