Case #1 Case #1 Endocrine Emergencies Endocrine Emergencies • 21-year old WF presents with dyspnea and abdominal pain. She has been complaining of thirst, polyuria, and blurred vision for a week while studying for final exams. She had a cold two David Bradley, MD weeks ago. Assistant Professor Division of Endocrinology, Diabetes, and Metabolism • HR 100, BP 100/60 supine, 90/50 upright The Ohio State University Wexner Medical Center • Ph Ex: flat neck veins, fruity breath, diffuse abdominal tenderness Case #1 Case #1 Pathogenesis of Diabetic Ketoacidosis (DKA) Pathogenesis of Diabetic Ketoacidosis (DKA) • Glucose 320 mg/dl Main Components: Main Components: • Bicarbonate 5 mEq/l HYPERGLYCEMIA HYPERGLYCEMIA MUSCLE ADIPOSE Glucose Glucose KETOSIS KETOSIS • Urine ketones 3+ Uptake Uptake ACIDOSIS ACIDOSIS Diabetic Ketoacidosis • Sodium 129 mg/dl • Sodium 129 mg/dl Proteolysis Proteolysis Lipolysis Li l i LIVER • Potassium 5.5 mmol/l Glycogenolysis Ketogenesis Gluconeogenesis • WBC 12,000/ m 3 • ECG: Sinus tachycardia CC BY-SA 3.0 • What is the diagnosis? Adipose image - Courtesy of Department of Histology, Jagiellonian University Medical College 1
Diabetic Ketoacidosis (DKA) Diabetic Ketoacidosis (DKA) Diabetic Ketoacidosis (DKA) Diabetic Ketoacidosis (DKA) Deficiency of insulin → • Increased hepatic glucose production → • Hyperglycemia Increased lipolysis → gluconeogenic precursors • (glycerol) to liver → gluconeogenesis → Hyperglycemia Increased proteolysis → gluconeogenic • precursors (amino acids) to the liver → ( i id ) t th li gluconeogenesis → Hyperglycemia Impaired glucose uptake in muscle and fat → • Hyperglycemia Increased lipolysis → FFA → ketone production • and ketoacidosis Glucagon excess → Increased glycogenolysis, • gluconeogenesis, and ketoacid production Porth’s Pathophysiology: Concepts of Altered Health States, 7 th ed. Lippincott Williams & Porth’s Pathophysiology: Concepts of Altered Health States, 7 th ed. Lippincott Williams & Wilkins, 2005 Wilkins, 2005 Diabetic Ketoacidosis (DKA) Diabetic Ketoacidosis (DKA) Symptoms and Signs of DKA Symptoms and Signs of DKA • Hyperventilation with • Polyuria Kussmaul respirations • Polydipsia • Fruity breath (Acetone) • Nausea and vomiting • Shock • Abdominal pain p • Signs of dehydration • Weakness Crude and age-adjusted death • Signs and symptoms • Depressed sensorium rates for hyperglycemic crises as underlying cause per related to precipitants • Blurry vision 100,000 diabetic population, United States, 1980 to 2009 Number (in thousands) of hospital discharges with diabetic ketoacidosis as first-listed diagnosis, United States, 1988 to 2009 Images from Centers for Disease Control and Prevention - www.cdc.gov 2
DKA Physical Examination DKA Physical Examination Precipitating factors for DKA Precipitating factors for DKA • Vital Signs: Tachycardia, tachypnea New-onset diabetes (20-25%) Endocrinopathies • • (metabolic acidosis), hypotension, Noncompliance with insulin Acromegaly • • therapy Thyrotoxicosis orthostasis • Cushing’s Syndrome Infection (30-40%) • • • Mental Status: Lethargy, coma (pneumonia and UTI most Trauma • • Dehydration: flat neck veins, dry mucous D h d ti fl t k i d common) common) Drugs D • Myocardial infarction Corticosteroids membranes • • Alcohol and/or drug abuse High dose thiazide • • • Respiratory: Deep, rapid respirations diuretics (Cocaine) (Kussmaul), fruity breath odor (acetone) Antipsychotics • Stroke • Hot weather and • Abdomen: Tenderness, guarding (may • Acute Pancreatitis • insufficient water mimic acute abdomen) Surgery • Laboratory Features Laboratory Features Additional Laboratory Additional Laboratory Diagnostic for DKA Diagnostic for DKA Features Consistent with DKA Features Consistent with DKA • Serum glucose > 250 mg/dL (13.9 • WBC count elevated (but < 25,000/mm 3 ) mmol/L) • Anion gap > 12 • PaCO < 40 mm • PaCO 2 < 40 mm • Arterial pH < 7.35 (venous pH <7.3) • Arterial pH < 7 35 (venous pH <7 3) • Na + normal or low • Serum bicarbonate < 18 mEq/L • Pseudohyponatremia • Serum acetone test positive • Measured serum K + high, normal, or low • Urinary ketone test positive (3+) • Triglycerides normal or elevated 3
DKA Additional Evaluation DKA Additional Evaluation Essential Management of DKA Essential Management of DKA • CBC with Differential • Urinalysis with Culture and Sensitivity • Appropriate intravenous fluid resuscitation • Chest X-Ray (“rule out pneumonia”) • Electrocardiogram El t di • Continuous insulin C i i li administration • If applicable: • Blood culture • Potassium replacement • Toxicology screen Image from CDC Public Health Image Library DKA Treatment (continued) DKA Treatment (continued) DKA Treatment DKA Treatment • If hypokalemic (<3.3), give K + before • IVF: 0.9% Normal saline at 15-20 mL/kg/lean insulin bolus body weight per hour (typically 1 liter/hour) • Patient is whole body potassium for the first 4 hrs depleted (300-600 mEq) due to gastrointestinal and renal (osmotic • Change IV fluid to Dextrose 5% 0.45% diuresis) losses diuresis) losses NaCl when glucose < 250 mg/dL • Hyperkalemia may occur due to insulin deficiency and acidosis (ICF to ECF) • IV drip: Regular human insulin (100 U/mL) • Potassium will drop rapidly once at 0.1-0.15 U/kg/hr (typically 5-10 U/h) insulin is given – promotes intracellular • Expect glucose to decrease by 75 K + entry mg/dL/hr • Initiate replacement when measured serum K + < 5.4 mmol/L 4
DKA: Signs of Recovery and DKA: Signs of Recovery and Case #2 Case #2 Transition off IV Insulin Transition off IV Insulin • 63-year-old WF presents with • Venous pH 7.3 obtundation. Her daughter had not • Arterial pH 7.35 seen her in a week, but she had been • Bicarbonate 18 mEq/L complaining of thirst and blurred • Anion gap 14 vision. • Patient tolerating PO intake • PMH: “Sugar diabetes” for which she • MUST give a dose of long-acting takes pills, HTN, arthritis insulin SQ, 120 minutes before • P Ex: HR 100, BP 100/60 supine stopping IV insulin drip • Overweight, flat neck veins Hyperosmolar Hyperglycemia Hyperosmolar Hyperglycemia Case #2 Case #2 Syndrome (HHS) Syndrome (HHS) • Glucose 600 mg/dl • Typically complication of type 2 diabetes • Bicarbonate 24 mEq/l • Older patients Hyperosmolar • Urine ketone: Trace positive • High mortality (up to 60%) Hyperglycemia • Sodium 145 mmol/l Sodium 145 mmol/l • Profound hyperglycemia (600-3000 mg/dL) • Profound hyperglycemia (600-3000 mg/dL) Syndrome Syndrome • Potassium 5.5 mmol/l • Hyperosmolality (> 320 mOsm/kg) • BUN 40, Creatinine 1.8 mg/dl • Severe dehydration • What is the diagnosis? • Often present with impaired mental status or coma 5
Hyperosmolar Hyperglycemia Hyperosmolar Hyperglycemia Comparison of DKA and Comparison of DKA and HHS HHS Syndrome (HHS) Syndrome (HHS) LIVER DKA HHS MUSCLE ↑ Gluconeogenesis *Glucose 250 to 800 600 to >1000 Glucose ↑ Glycogenolysis Osmolarity Variable >320 Uptake **Urinary ketones ++ Trace + or negative **BHB + - pH < 7.3 >7.3 HYPERGLYCEMIA HYPERGLYCEMIA HYPERGLYCEMIA HYPERGLYCEMIA Bicarbonate <18 >18 HYPEROSMOLALITY HYPEROSMOLALITY **Anion Gap >15 <15 Precipitating illness Yes Yes Mortality + ++ KIDNEYS Age Young Elderly PANCREAS Glucose *Two factors contribute to less severe hyperglycemia in DKA: Author: Glucose Earlier presentation of symptoms Mikael Häggström Excretion Younger patients have a higher GFR and more glucosuria Toxicity ** Absence of ketogenesis in HHS due to relative as opposed to absolute insulin deficiency Case #3 Case #3 Management of HHS Management of HHS • Intravenous fluid resuscitation • 45-year old WM with type 1 diabetes is • Isotonic fluid (0.9% NaCl) initially admitted for R/O MI. Started on NPH BID and sliding scale Humalog QAC and HS. • Hypotonic fluid (0.45% NaCl) when BP stabilizes • At 10:30 pm, patient calls nurse reporting that he feels “funny.” th t h f l “f ” • Add Dextrose 5% when glucose 250 mg/dL • At 11:00 pm, nurse finds patient diaphoretic and mumbling incoherently. • Insulin administration • What is the diagnosis? • Similar to DKA • May wait until hemodynamically stable Hypoglycemia • Avoid over-correction of glucose 6
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