PATH1016 Diabetes 2024-2025 PDF

Diabetes Mellitus PATH1016 PATH1016_Diabetes 2024-2025 1 The Pancreas – Normal Anatomy REVIEW Two functions of the Pancreas 1. Exocrine 2. Endocrine Exocrine c...

Diabetes Mellitus PATH1016 PATH1016_Diabetes 2024-2025 1 The Pancreas – Normal Anatomy REVIEW Two functions of the Pancreas 1. Exocrine 2. Endocrine Exocrine cells secrete digestive enzymes & bicarb into the duodenum Acini cells Endocrine cells secrete insulin and glucagon for regulation of blood glucose levels The Pancreas, illustration. Photograph. Britannica ImageQuest, Encyclopædia Islets of Langerhans Britannica, Aug 31 2017. quest-eb- com.gbcprx01.georgebrown.ca/images/132_1479712. Accessed 11 Oct 2024. PATH1016_Diabetes 2024-2025 2 Terms – the four “G”s Gluconeogenesis Creation of glucose from sources other than carbohydrates Proteins, glycerol or lactate Glycogenesis Creation of Glycogen Glycogen is a carbohydrate that is easily transformed into simple glucose Glycolysis The breakdown of glucose with an individual cell to release energy in the form of ATP Glycogenolysis Breakdown of glycogen to simple glucose PATH1016_Diabetes 2024-2025 3  Glucose- Regulating Hormones and their effects. Major hormones and their effects. Illustration. Britannica ImageQuest, Encyclopædia Britannica, 25 May 2016. quest-eb- com.gbcprx01.georgebrown.ca/images/309_366465. Accessed 11 Oct 2024. PATH1016_Diabetes 2024-2025 4  Insulin-Stimulated Glucose Uptake Insulin Drives glucose INto the cells Produced in the Beta cells of Pancreas Glucose transporter - cell membranes are impermeable to glucose Promotes uptake of glucose into cells and its storage as glycogen (glycogenesis), fat (in adipose tissue) and protein Will also stimulate glucose breakdown Norris, T. L. (2019-10-17). Porth's Essentials of Pathophysiology, 5th Edition. [[VitalSource Bookshelf version]]. Retrieved from for energy within a cell (glycolysis) vbk://9781975151812 PATH1016_Diabetes 2024-2025 5 Insulin Main Actions Promotes glucose uptake by target cells and provides for glucose storage as glycogen Prevents fat breakdown (lipolysis) and glycogen breakdown (glycogenolysis) Inhibits gluconeogenesis and increases protein synthesis Goal of insulin: Reduce blood glucose so that is why it promotes storage and breakdown. PATH1016_Diabetes 2024-2025 6  Glucagon Made in the Alpha cells Is for when the glucose is GONe Mnemonic Is your glucose gone? Get GLUCAGON! Glucagon will RAISE your glucose in a flash! 1. It stimulates the release of glucose into your blood when fasting 2. Liver is prime storage depot 3. Increases Glycogenolysis (breakdown of glycogen to glucose) PATH1016_Diabetes 2024-2025 7 Insulin and Glucagon Glucagon inhibits Glycolysis? In starvation the goal is to protect the brain and heart The goal of glucagon is to mobilize glucose stores from the liver so that this glucose can be sent to the brain and heart Also increases transport of amino acids to liver to stimulate gluconeogenesis. Insulin and glucagon work in concert to maintain normal blood sugar concentration PATH1016_Diabetes 2024-2025 8 Counter regulatory hormones Hormones that affect blood Counteract storage functions glucose of insulin to reduce the depletion of serum glucose Catecholamine Fasting Growth hormone Exercise Glucocorticoids Illness (fever) PATH1016_Diabetes 2024-2025 9  Diabetes Mellitus Diabetes mellitus is an abnormality in blood glucose regulation and nutrient storage related to an absolute deficiency in insulin or resistance to the actions of insulin: Decreased insulin secretion Insensitivity to insulin (Target cell resistance) Characterized by hyperglycemia Classifications of diabetes include Type 1, Type 2 Gestational DM PATH1016_Diabetes 2024-2025 10 Type 1 Diabetes Mellitus Complete loss of production of insulin Age: Most 25yrs age but incidence increasing in adolescents, paralleling increasing rate of obesity in children and adolescents Insulin resistance (metabolic) by body cells Risk of development is correlated to Age Obesity – effect on tissue sensitivity to insulin Genetic (family history) and acquired environmental factors in causing Type 2 DM. PATH1016_Diabetes 2024-2025 13 Type 2 Diabetes Mellitus - Pathogenesis Metabolic abnormalities include: 1. Insulin resistance 2. Increased glucose production by the liver 3. Deranged (or decreased) secretion of insulin by the pancreatic beta cells Decrease in beta cell mass Increase in apoptosis Exhaustion FIGURE 41-18 Pathogenesis of type 2 diabetes mellitus. Glucotoxicity and lipotoxicity Norris, T. L. (2019-10-17). Porth's Essentials of Pathophysiology, 5th Edition. [[VitalSource Bookshelf version]]. Retrieved from vbk://9781975151812 PATH1016_Diabetes 2024-2025 14 Metabolic Syndrome and Insulin Resistance Features of the syndrome include: 1.Abdominal obesity 2.Hyperglycemia 3.Hypertension 4.Hyperlipidemia PATH1016_Diabetes 2024-2025 15 Role of adipose tissue in Type 2 DM Increase in Free fatty acids (FFAs) Excess, chronic elevation of FFAs ➞cause pancreatic beta cell dysfunction (lipotoxicity) FFAs inhibit glucose uptake & glycogen storage Accumulation of FFAs & triglycerides ➞ Reduce hepatic insulin sensitivity Leads to ↑↑ hepatic glucose production & hyperglycemia PATH1016_Diabetes 2024-2025 16 Gestational Diabetes Mellitus (GDM) ▪Any degree of glucose intolerance that begins during pregnancy. ▪Occurs in 5-10% of pregnancies but is increasing. ▪Risk factors: ▪Glycosuria ▪Strong family history of Type 2 DM ▪Obesity ▪Polycystic ovary disease ▪Prior history of gestational diabetes ▪Previous delivery of a large-for-gestational age infant PATH1016_Diabetes 2024-2025 17 Gestational Diabetes Mellitus Gestational Diabetes Mellit Image is one of the most recent libraries health magazine. Search more Diabetes and images referrals for obtaining appropriate treatment for diese. Placenta produces hormones to: -Help shift nutrients from mother to fetus -Prevent development of low blood glucose of mother Placenta hormones resist insulin action & lead to higher glucose levels In attempt to decrease glucose levels, mother’s body tries to increase insulin production (3X) If the pancreas cannot produce enough insulin, gestational diabetes results PATH1016_Diabetes 2024-2025 18  Gestational Diabetes Screening Risk assessment for GDM carries high Risk for all pregnant women complications of pregnancy, at first prenatal visit mortality and fetal abnormalities. If High risk: If average or low risk Glucose testing is for GDM: done ASAP Oral glucose tolerance test (OGTT) is done at 24-28 weeks gestation PATH1016_Diabetes 2024-2025 19 Gestational Diabetes Fetal abnormalities include Macrosomia Hypoglycemia Hypocalcemia Polycythemia Hyperbilirubinemia. PATH1016_Diabetes 2024-2025 20  Treatment of Gestational Diabetes Close observation of mother and fetus: Maternal fasting & postprandial blood glucose monitoring Frequent fetal growth measurements Observe for signs of fetal distress Dietary alterations Insulin therapy If dietary changes do not sufficiently reduce blood glucose levels PATH1016_Diabetes 2024-2025 21 Maternal follow-up from gestational diabetes On-going follow-up required after delivery to detect Type II DM early Evaluated during first postpartum visit with a 2hour OGTT with a 75g glucose load. Prognosis: 50% will develop Type 2 diabetes within 5-10 years. PATH1016_Diabetes 2024-2025 22  Has short-term and long- Hyperglycemia term effects Most commonly identified short term signs and symptoms include the three polys Clinical manifestations Polyuria (excessive urination) of diabetes Polydipsia (excessive thirst) Polyphagia (excessive hunger) PATH1016_Diabetes 2024-2025 23  Rational for the “Polys” Diabetes is referred to as “starvation in the midst of plenty” Plenty of glucose that cannot be moved into cells to be used Instead, glucose stays in blood and is excreted through kidneys Therefore Ineffective use of glucose leads to weight loss and increased appetite (polyphagia) Elevated blood glucose make the blood HYPERTONIC that creates an osmotic pressure that sucks water into the vascular space which leads to increased urination (polyuria) and thirst (polydipsia) PATH1016_Diabetes 2024-2025 24 Clinical Weight loss Blurred vision manifestations of diabetes Fatigue Paresthesias Weakness Chronic infections PATH1016_Diabetes 2024-2025 25  Type 2 DM: Clinical Manifestations Osmotic Person may go Nonspecific fluid/electrolyte many years with symptoms May Gradual onset loss from undetected have classic hyperglycemia may hyperglycemia symptoms of type 1 become severe Recurrent Recurrent vaginal Prolonged wound Fatigue infections yeast infection healing Visual acuity Painful peripheral changes neuropathy in feet PATH1016_Diabetes 2024-2025 26 Diagnostic tests for diabetes Diagnosis confirmed through laboratory tests that measure blood glucose levels. 1. Fasting plasma glucose 2. Casual blood glucose test 3. Oral glucose tolerance test (OGTT) 4. Capillary blood glucose monitoring 5. Glycosylated hemoglobin (HbA1C) PATH1016_Diabetes 2024-2025 27  Diabetes management Desired outcome of glycemic control in both type 1 and type 2 diabetes is normalization of blood glucose as a means of preventing short- and long-term complications. Treatment plans involve: 1. Dietary management 2. Exercise 3. Antidiabetic agents Oral antidiabetics (Type 2 DM) Injections (Type 1 & Advanced Type 2 DM) PATH1016_Diabetes 2024-2025 28  Insulin therapy Insulin administered by injection or SC infusion Schedule mimics the body's normal insulin secretion patterns Type 1 DM- always require insulin replacement Type 2 DM- eventually will require insulin. Key types of insulin are classified by duration & peak of action 1. Fast acting 2. Intermediate acting 3. Long acting May use combination of different types PATH1016_Diabetes 2024-2025 29 Acute complications of diabetes Three major acute complications of impaired glucose regulation 1. Diabetic ketoacidosis (DKA) 2. Hyperosmolar hyperglycemic state (HHS) 3. Hypoglycemia All are life-threatening and require immediate recognition and intervention!!! PATH1016_Diabetes 2024-2025 30 Diabetic Ketoacidosis (DKA) Lack of insulin results in rapid breakdown of energy stores from muscle and fat Leads to increased movement of amino acids to the liver to be converted into glucose and for fatty acids to be converted to ketones. In the presence of ketosis, increased counter-regulatory hormones are released leading to hyperglycemia PATH1016_Diabetes 2024-2025 31 Diabetic Ketoacidosis (DKA) Hyperglycemia WITH Metabolic Ketoacidosis Osmotic diuresis, dehydration and a critical loss of electrolytes occurs Fluid shifts lead to hyperkalemia Metabolic acidosis requires buffering by bicarbonate ions. Clinical diagnosis includes 1. hyperglycemia (>13.8 mmol/L) 2. low serum bicarbonate 3. low arterial pH 4. positive ketones (urine & blood) PATH1016_Diabetes 2024-2025 32 DKA Manifestations Breath has a fruity Hypotension and smell because of the tachycardia may be presence of volatile present because of ketoacids (acetone decrease in blood breath) volume. Heart rate increases Rate and depth of respiration increases (Kussmauls’ respirations) PATH1016_Diabetes 2024-2025 33 DKA Treatment Goals Improve circulatory volume and tissue perfusion IV fluids Decrease blood glucose Insulin infusion Correct acidosis Correct electrolyte imbalance Potassium in fluids PATH1016_Diabetes 2024-2025 34 Hypoglycemia Occurs from an excess of insulin in the blood resulting in below-normal blood glucose levels. Affects both Type 1 & 2 treated with insulin injections Causative factors include: error in insulin dose failure to eat increased exercise decreased insulin need after removal of stressful situation medication changes change in insulin injection site PATH1016_Diabetes 2024-2025 35  Clinical manifestations of hypoglycemia Signs and symptoms divided into two categories: Altered cerebral function: Brain’s main energy source = glucose Headache difficulty in problem solving altered behavior coma seizures. Activation of the autonomic nervous system Hunger at onset due to activation of PNS PNS response activates SNS Anxiety Tachycardia Sweating cool, clammy skin PATH1016_Diabetes 2024-2025 36 Treatment of When sugar is GONE….. hypoglycemia Most effective treatment is immediate administration of 15 to 20 g of glucose in a concentrated SIMPLE carbohydrate source. If person is unconscious or unable to swallow, glucagon can be given intramuscularly or subcutaneously. PATH1016_Diabetes 2024-2025 37  Chronic Complications of Diabetes Mellitus Microvasculature Macrovasculature Foot ulcers complications complications Neuropathies Coronary artery (CAD) Nephropathies Cerebral vasculature Retinopathies (Stroke) Peripheral vascular disease (PVD) PATH1016_Diabetes 2024-2025 38 Neuropathies Two pathologic changes 1. Thickening of the wall of the nutrient vessels that supply the nerves leading to the assumption of ischemia. 2. Segmental demyelination process that affects the Schwann cell resulting in a slowing of nerve conduction. PATH1016_Diabetes 2024-2025 39  Diabetic Nephropathies Describes the combination of lesions that occur concurrently in the diabetic kidney. Leading cause of chronic kidney disease (CKD) in person starting renal replacement therapy (RRT). Risk factors include; Genetic and familial predisposition Elevated blood pressure Poor glycemic control Smoking Hyperlipidemia Microalbuminuria PATH1016_Diabetes 2024-2025 40  Glomerular changes in kidney Kidney enlargement nephron hypertrophy and hyperfiltration reflect increasing work performed by the kidneys in resorbing excessive amounts of glucose. Diabetic First manifestation is increase in urinary Nephropathies albumin excretion (microalbuminuria). Hypertension accelerates the progression of diabetic nephropathy. Leads to Chronic Kidney Disease (CKD to ESRD) PATH1016_Diabetes 2024-2025 41  Treatment for Diabetic Nephropathy Glycemic control Maintenance of blood pressure control (