Pathology: Week #10 - Diabetes Mellitus PDF

PATHOLOGY: WEEK #10 – Diabetes Mellitus The Pancreas Will also stimulate glucose breakdown Two functions of the Pancreas for energy within a cell (glycolysis). o Exocrine Cells - secrete digestive Insulin...

PATHOLOGY: WEEK #10 – Diabetes Mellitus The Pancreas Will also stimulate glucose breakdown Two functions of the Pancreas for energy within a cell (glycolysis). o Exocrine Cells - secrete digestive Insulin Main Actions enzymes & bicarb into the Promotes glucose uptake by target cells duodenum and provides for glucose storage as ▪ Acini cells glycogen o Endocrine Cells - secrete insulin Prevents fat breakdown (lipolysis) and and glucagon for regulation of glycogen breakdown (glycogenolysis) blood glucose levels Inhibits gluconeogenesis and increases ▪ Islets of Langerhans protein synthesis The Four G’s o Goal of insulin: Reduce blood Gluconeogenesis glucose so that is why it promotes o Creation of glucose from sources storage and breakdown. other than carbohydrates Glucagon o Proteins, glycerol or lactate Made in the Alpha cells Glycogenesis Is for when the glucose is GONe o Creation of Glycogen Mnemonic o Glycogen is a carbohydrate that is o Is your glucose gone? Get easily transformed into simple GLUCAGON! Glucagon will RAISE glucose your glucose in a flash! Glycolysis It stimulates the release of glucose into o The breakdown of glucose with an your blood when fasting individual cell to release energy in Liver is prime storage depot the form of ATP Increases Glycogenolysis (breakdown of Glycogenolysis glycogen to glucose) o Breakdown of glycogen to simple Insulin and Glucagon glucose Does Glucagon inhibit Glycolysis? Glucose – regulating hormones and their effects In starvation the goal is to protect the brain and heart Pancreas – Islet of Langerhans The goal of glucagon is to mobilize o Glucagon and Insulin glucose stores from the liver so that this ▪ Glucagon – Liver – Release glucose can be sent to the brain and heart Glucose in the blood Also increases transport of amino acids ▪ Insulin - to liver to stimulate gluconeogenesis. Liver/Adipose/Muscle – Insulin and glucagon work in concert to Absorption of glucose from maintain normal blood sugar blood concentration. Insulin-Stimulated Glucose Uptake Counter regulatory hormones Insulin - Drives glucose INto the cells Produced Hormones that affect blood glucose in the Beta cells of Pancreas. o Catecholamine Glucose transporter - cell membranes o Growth hormone are impermeable to glucose o Glucocorticoids Promotes uptake of glucose into cells Counteract storage functions of insulin and its storage as glycogen to reduce the depletion of serum (glycogenesis), fat (in adipose tissue) and glucose protein o Fasting o Exercise  PATHOLOGY: WEEK #10 – Diabetes Mellitus o Illness (fever) --------------------------------------- Diabetes Mellitus Risk of development is correlated to: - Diabetes mellitus is an abnormality in OGA blood glucose regulation and nutrient o Obesity – effect on tissue storage related to an absolute deficiency sensitivity to insulin in insulin or resistance to the actions of o Genetic (family history) and insulin: acquired environmental factors in o Decreased insulin secretion causing Type 2 DM o Insensitivity to insulin (Target cell o Age resistance) Type 2 Diabetes Mellitus – Pathogenesis o Characterized by hyperglycemia Metabolic abnormalities include: o Classifications of diabetes include o Insulin resistance Type 1, Type 2 Gestational DM o Increased glucose production by --------------------------------------- the liver Type 1 Diabetes Mellitus o Deranged (or decreased) Complete loss of production of insulin secretion of insulin by the Age: Most 25yrs age but o Hypertension incidence increasing in adolescents, o Hyperlipidemia paralleling increasing rate of obesity in Role of adipose tissue in Type 2 DM children and adolescents 1. Increase in Free fatty acids (FFAs) Insulin resistance (metabolic) by body cells  PATHOLOGY: WEEK #10 – Diabetes Mellitus 2. Excess, chronic elevation of FFAs ➞cause ▪ Oral glucose tolerance pancreatic beta cell dysfunction test (OGTT) is done at 24-28 (lipotoxicity) weeks gestation 3. FFAs inhibit glucose uptake & glycogen Gestational Diabetes storage Fetal abnormalities include 4. Accumulation of FFAs & triglycerides ➞ o Macrosomia Reduce hepatic insulin sensitivity o Hypoglycemia 5. Leads to ↑↑ hepatic glucose production & o Hypocalcemia hyperglycemia o Polycythemia --------------------------------------- o Hyperbilirubinemia Gestational Diabetes Mellitus (GDM) Treatment of Gestational Diabetes Any degree of glucose intolerance that Close observation of mother and fetus: begins during pregnancy. o Maternal fasting & postprandial Occurs in 5-10% of pregnancies but is blood glucose monitoring increasing. o Frequent fetal growth Risk factors: measurements o Glycosuria o Observe for signs of fetal distress o Strong family history of Type 2 DM Dietary alterations o Obesity Insulin therapy o Polycystic ovary disease o If dietary changes do not o Prior history of gestational diabetes sufficiently reduce blood glucose o Previous delivery of a large-for- levels gestational age infant Maternal follow-up from gestational diabetes Gestational Diabetes Mellitus On-going follow-up required after 1. Placenta produces hormones to: delivery to detect Type II DM early o Help shift nutrients from mother o Evaluated during first postpartum to fetus visit with a 2hour OGTT with a 75g o Prevent development of low glucose load. blood glucose of mother Prognosis: 2. Placenta hormones resist insulin action o 50% will develop Type 2 diabetes & lead to higher glucose levels within 5-10 years. 3. In attempt to decrease glucose levels, --------------------------------------- mother’s body tries to increase insulin Clinical manifestations of diabetes production (3X) 1. Hyperglycemia Has short-term and long- 4. If the pancreas cannot produce enough term effect insulin = gestational diabetes results 2. Most commonly identified short term Gestational Diabetes Screening signs and symptoms include the three GDM carries high Risk for complications polys of Fetal Abnormalities, Pregnancy, and a. Polyuria (excessive urination) Mortality. FAPM b. Polydipsia (excessive thirst) Risk assessment for all pregnant women c. Polyphagia (excessive hunger) at first prenatal visit 3. Weight loss o If High risk: Glucose testing is 4. Blurred vision done ASAP 5. Paresthesias o If average or low risk for GDM: 6. Fatigue Weakness 7. Chronic infections RATIONALE for POLY’s  PATHOLOGY: WEEK #10 – Diabetes Mellitus Diabetes is referred to as “starvation in the midst of plenty” Key types of insulin are classified by Plenty of glucose that cannot be moved duration & peak of action into cells to be used 1. FAST acting Instead, glucose stays in blood and is 2. INTERMEDIATE acting excreted through kidneys 3. LONG acting Therefore ▪ May use combination of o Ineffective use of glucose leads to different types weight loss and increased appetite --------------------------------------- (polyphagia) ACUTE COMPLICATIONS of DIABETES o Elevated blood glucose make the Three major acute complications of blood HYPERTONIC that creates impaired glucose regulation an osmotic pressure that sucks 1. Diabetic ketoacidosis (DKA) water into the vascular space 2. Hyperosmolar hyperglycemic state which leads to increased urination (HHS) (polyuria) and thirst (polydipsia) 3. Hypoglycemia Diagnostic tests for diabetes --------------------------------------- Diagnosis confirmed through laboratory tests DIABETIC KETOACIDOSIS that measure blood glucose levels. Lack of insulin results in rapid 1. Fasting plasma glucose breakdown of energy stores from muscle 2. Casual blood glucose test and fat 3. Oral glucose tolerance test (OGTT) Leads to increased movement of amino 4. Capillary blood glucose monitoring acids to the liver to be converted into 5. Glycosylated hemoglobin (HbA1C) glucose and for fatty acids to be Diabetes management converted to ketones. Desired outcome of glycemic control in In the presence of ketosis, increased both type 1 and type 2 diabetes is counter-regulatory hormones are normalization of blood glucose as a released leading to hyperglycemia means of preventing short- and long- DKA MANIFESTATIONS term complications. Treatment plans Breath has a fruity smell because of the involve: DEA presence of volatile ketoacids (acetone 1. Dietary management breath) 2. Exercise Hypotension and tachycardia may be 3. Antidiabetic agents present because of decrease in blood a. Oral antidiabetics (Type 2 DM) volume. b. Injections (Type 1 & Advanced Heart rate increases Type 2 DM Rate and depth of respiration increases --------------------------------------- (Kussmauls’ respirations) INSULIN THERAPY DKA TREAMENT GOALS Insulin administered by injection or SC Improve circulatory volume and tissue infusion. perfusion 1. Schedule mimics the body’s o IV fluids normal insulin secretion patterns Decrease blood glucose ▪ Type 1 DM – ALWAYS o Insulin infusion require insulin replacement Correct acidosis ▪ Type 2 DM – EVENTUALLY Correct electrolyte imbalance will require insulin o Potassium in fluids  PATHOLOGY: WEEK #10 – Diabetes Mellitus --------------------------------------- CHRONIC COMPLICATIONS of DM HYPOGLYCEMIA Microvasculature complications Occurs from an excess of insulin in the o Neuropathies blood resulting in below-normal blood o Nephropathies glucose levels. o Retinopathies Affects both Type 1 & 2 treated with Macrovasculature complications insulin injections o Coronary artery (CAD) Causative factors include: o Cerebral vasculature (Stroke) o error in insulin dose o Peripheral vascular disease (PVD) o failure to eat Foot ulcers o increased exercise --------------------------------------- o decreased insulin need after Neuropathies removal of stressful situation Two pathologic changes o medication changes o Thickening of the wall of the o change in insulin injection site nutrient vessels that supply the CLINICAL MANIFESTATIONS OF nerves leading to the assumption HYPOGLYCEMIA of ischemia. Signs and symptoms divided into two o Segmental demyelination categories: process that affects the Schwann Altered cerebral function: Brain’s main cell resulting in a slowing of nerve energy source = glucose conduction. 1. Headache --------------------------------------- 2. difficulty in problem solving DIABETIC NEPHROPATHIES 3. altered behavior Describes the combination of lesions 4. coma that occur concurrently in the diabetic 5. seizures kidney. Activation of the autonomic nervous Leading cause of chronic kidney system disease (CKD) in person starting renal 1. Hunger at onset due to activation replacement therapy (RRT). of PNS Risk factors include; 2. PNS response activates SNS o Genetic and familial predisposition ▪ Anxiety o Elevated blood pressure ▪ Tachycardia o Poor glycemic control ▪ Sweating o Smoking ▪ cool, clammy skin o Hyperlipidemia TREATMENT of HYPOGLYCEMIA o Microalbuminuria When sugar is GONE... Glomerular changes in kidney Most effective treatment is immediate Kidney enlargement administration of 15 to 20 g of glucose in o Nephron hypertrophy and a concentrated SIMPLE carbohydrate hyperfiltration reflect increasing source. work performed by the kidneys in If person is unconscious or unable to resorbing excessive amounts of swallow, glucagon can be given glucose. intramuscularly or subcutaneously. The first manifestation is the increase in --------------------------------------- urinary albumin excretion (microalbuminuria).  PATHOLOGY: WEEK #10 – Diabetes Mellitus Hypertension accelerates the progression Macrovascular complications of diabetic nephropathy. Diabetes mellitus major risk factor for: Leads to Chronic Kidney Disease (CKD to o atherosclerotic coronary artery ESRD) disease (CAD) TREATMENT for DIABETIC NEPHROPATHY o cerebrovascular disease (Stroke) Glycemic control o peripheral vascular disease (PVD) Maintenance of blood pressure control Increased 2 to 4 times in people with (