1. Diabetic Emergencies

2. Introduction: Endocrine System Endocrine System controls Many body Functions, by Releasing Hormones Hormones –Chemicals that Affect Endocrine Glands or Body Systems as well as ability to think with any clarity at all. Endocrine –Release hormones directly into the blood which transport hormones to target tissue Exocrine –Transport hormones to target tissue via ducts

3. Anatomy and Physiology: Endocrine System Endocrine Pancrease – Located behind the stomach between the spleen and duodenum – Islets of Langerhans  cells – glucagon  cells – insulin  cells – somatostatin/gastrin

4. Anatomy and Physiology: Endocrine System Adrenal Glands – Pyramid shaped organs, retroperitoneal, superior to each Kidney. Adrenal Cortex – Glucocorticoids – Mineralocorticoids – Androgens/Estrogens Adrenal Medulla – Epinephrine – Norepineprhrine

5. Physiology: Carbohydrate Metabolism Terms: –Coupled Reactions – chemical reaction occurs in specific organ system allowing it to complete it’s function –Free Energy – amount of energy released by complete oxidation of food

6. Physiology: Carbohydrate Metabolism Adenosine Triphosphate (ATP) –Present in all cells Adenine – Ribose – 3 phosphate radicals –Intermediary compound in coupled reactions Reactions allowing energy extraction from food Reactions in many physiological functions –90+% of carbohydrates in the body are used for ATP formation

7. Physiology: Carbohydrate Metabolism ATP (cont.) –ADP –AMP Guyton Medical Physiology

8. Physiology: Carbohydrate Metabolism Role of Glucose in Metabolism –Carb digestion = glucose (80%), fructose, galactose –Liver converts fructose/galactose to glucose ATP involved Glucose transport –Transport across cell membrane occurs through facilitated diffusion Glucose carrier protein –Facilitated by insulin (10+x)

9. Physiology: Carbohydrate Metabolism Role of Insulin –Hormone Binds w/ muscle/adipose cell membrane receptors Increased permeability to glucose Plasma ½ life of ~6 minutes

10. Physiology: Carbohydrate Metabolism Glucose Phosphorylation (glucose 6-phosphate) –Serves to capture glucose in the cell Glucokinase/hexokinase + ATP Glycogenesis –Occurs if glucose not immediately used for energy Glycogen = stored glucose Mostly in liver and muscle tissue

11. Physiology: Carbohydrate Metabolism Glycogenolysi s –glycogen back to glucose –Phosphorylas e Activated by Epinephrine and Glucagon –Form cAMP which leads to activation of phosphory lase

12. Physiology: Carbohydrate Metabolism Release of energy from Glucose – Stage 1 –Glycolysis – 10 step process 2 pyruvic acid 2 ATP 4 Hydrogen

13. Physiology: Carbohydrate Metabolism Release of energy from Glucose – Stage 2 –Pyruvic Acid acetyl CoA

14. Physiology: Carbohydrate Metabolism Release of energy from Glucose – Stage 3 –Krebs cycle (citric acid cycle) Results in 4CO 2 + 16H + 2CoA + 2ATP

15. Physiology: Carbohydrate Metabolism Oxidative Phosphorylation –Oxidative reactions occur to form large quantities of ATP (water as waste)

16. Physiology: Carbohydrate Metabolism Summary of ATP Formation (1 mole of glucose) –Glycolysis = 4 molecules 2 molecules used for initial phosphorylation Net result = 2 ATP –Kreb’s Cycle = 2 molecules 1 revolution = 1 ATP 1 glucose molecule = 2 revolutions Net result = 2 ATP –Oxidative phosphorylation 24 H + atoms released during glycolysis 20 oxidized w/ 3 ATP released for every 2 H + Remaining 4 H + oxidized in stage 2 Net result = 34 ATP 438,000 calories/66% : remaining calories lost as heat

17. Physiology: Carbohydrate Metabolism Anaerobic glycolysis –ATP via glycolysis does not require O 2 –97% wasted energy via this method : 24,000 calories produced ‘waste’ product is lactic acid Can be reconverted to pyruvic acid when O 2 available again Energy source during heavy exercise for myocardial cells

18. Physiology: Carbohydrate Metabolism Gluconeogenesis –Formation of glucose from glycerol and amino acids –Regulated by low BGL and decreased carbohydrate stores Release of cortisol from adrenal cortex –Mobilizes amino acids to form glucose in the liver

19. Physiology: Lipid Metabolism New Line Cinemas

20. Physiology: Lipid Metabolism Triglycerides and Energy  Hydrolysis – glycerol + fatty acids Glycerol enters glucolytic pathway  Fatty acid utilization Carried into mitochondria via carnitine  Beta Oxidation Fatty acid degraded to acetyl-CoA

21. Beta Oxidation Acetyl-CoA produced enters the Kreb’s cycle –Results in ATP and Hydrogen –134 ATP produced for complete oxidation of fat molecule(stearic acid)

22. Physiology: Lipid Metabolism Ketosis –By product of lipid metabolism Acetoacetic acid Acetone β-hydroxybutyric acid –Occurs in Starvation (no glucose) IDDM (no insulin for glucose trnx) High fat diet (no glucose)

23. Endocrine Emergencies: Diabetes Mellitus Diabetes Mellitus –Carbohydrate utilization is reduced while that of lipid and protein is enhanced. Caused by insulin deficiency.

24. Insulin actions Increase membrane permeability Increase glucose phosphorylation Increase glycogenesis Increase fat synthesis (glycerol) Suppress glucagon and epinephrine release

25. Falling blood glucose levels Glucagon released: glycogenolysis Epinephrine/norepi released: fat metabolism enhanced>glycogenolysis Cortisol : fat metabolism Growth hormone : enhanced Insulin production and release inhibited

26. Endocrine Emergencies: Diabetes Mellitus Type I: Insulin Dependent Diabetes Mellitus (IDDM) – Results from destruction of the insulin producing β cells of the pancreas. Evidence also suggests an increase in glucagon production by the α cells – Peak onset in ages 11 and 13 (often referred to as Juvenile onset diabetes). New onset over 30 very rare – Etiology differs; may be viral, environmental, and/or genetic. New cases usually occur in the fall and spring – Symptom onset abrupt – Prone to Ketoacidosis

27. Endocrine Emergencies: Diabetes Mellitus Type I: IDDM –Clinical Presentation Polydipsia -  BGL = intracellular dehydration and hypothalamus thirst response Polyuria -  BGL = Glycosuria and osmotic diuresis Polyphagia -  cellular carbohydrate, fat, and protein = cellular starvation Weight loss – Due to loss of body fluid and tissue Fatigue – Poor use of food products

28. Endocrine Emergencies: Diabetes Mellitus Type II: Non-Insulin Dependent Diabetes Mellitus (NIDDM) – May have normal insulin levels and/or β cells. Characterized by poor utilization of insulin – Generally occurs over 40 years of age. Accounts for most cases. If you’re of Pima Indian descent, sucks to be you – Patient is usually obese, suffering end- organ complications – 3 times more prevalent in adults w/ lower socioeconomic/education status – Increased incidence in women with higher parity

29. Endocrine Emergencies: Diabetes Mellitus Pathology of Diabetes Mellitus –Chronic/acute Dehydration Cellular Osmotic diuresis (urinary sugar) –Acidosis Increase in keto acids Hyponatremia due to excretion of keto acids

30. Endocrine Emergencies: Diabetes Mellitus End-Organ Complications of Diabetes – Accelerated atherosclerosis with medial calcification –Microvascular disease; abnormal function of capillary basement membrane –Diabetic neuropathy; Autonomic dysfunction; Demyelination – Abnormalities of Schwann’s cells

31. Endocrine Emergencies: Hypoglycemia Hypoglycemia Defined Fall in blood glucose concentrations that elicits symptoms of glucose deprivation in the central nervous system. Sudden (Adrenergic sx) Diaphoresis, pallor Tremulousness Tachycardia, palpitations Visual distubances Mental confusion, weakness, Gradual Fatigue Confusion Headach Memory loss Seizures, coma

32. Endocrine Emergencies: Hypoglycemia Pathophysiology Spontaneous Hypoglycemia –Alimentary (gut defect, GI surgery, etc.) –Early diabetes (new onset Type II) –Idiopathic hypoglycemia –Fasting –-Islet-cell tumor –-Extrapancreatic neoplasms –-Endocrine related –-Hepatic disease Induced Hypoglycemia –-Insulin induced –-Factitious –-Sulfonylureas (oral hypoglycemic agents) –-Alcohol – -Misc. drugs (ASA, etc.)

33. Endocrine Emergencies: Diabetes Mellitus/Hypoglycemia Prehospital Management of Diabetic Emergencies  ABC’s/O2  Ascertain history from patient and/or family/bystanders  Determine BGL (Normal range 60-120 mg/Dl)  Oral Glucose if BGL <60 and patient conscious.  If unable to take orally, est. IV and administer 25 g D50/W  Child 0.5 g/kg  If unable to est. IV or orals, Glucagon 1 mg SC/IM  Repeat glucoscan after glucose administration Transport all patients on oral anti-hypoglycemic agents who develop hypoglycemia In general, give IV D50/W for any hypoglycemia <50 even if oral glucose given

34. Endocrine Emergencies: Ketoacidosis Defined –Absolute or relative deficiency of insulin and increase in insulin counterregulatory hormones (Epi, cortisol, glucagon, growth hormone) –Hepatic glucose production & fat mobilization increases, peripheral glucose usage decreases and ketogenesis is stimulated.

35. Endocrine Emergencies: Ketoacidosis Clinical Manifestations –Polyuria, dehydration –Sodium, Phosphorous, Magnesium deficits –May have profound hypokalemia Signs and symptoms –Kussmaul respirations –Postural dizzyness –CNS depression –Ketonuria –Anorexia –Nausea –Abdonminal pain –Thirst, polyuria Treatment: Altered mentation protocol Fluid challenge

36. Endocrine Emergencies: Hyperosmolar Syndrome Hyperosmolar Hyperglycemic Nonketotic Syndrome –Common in type 2 diabetics –Characterized by lack of ketosis –Serum glucose higher than DKA Clinical Manifestations –Glucosuria/polyuria due to ↑ glucose –Neurologic changes Treatment –Significant fluid and electrolyte replacement –Pt’s have a higher mortality

37. Somogyi Effect Rebound hyperglycemia –Counterregulatory hormones activate gluconeogenesis and glycogenolysis –Hormones supress insulin 12-48 hours –Also influenced by excessive carb intake

38. Common Prescription Medications Oral agents –Sulfonylureas -  insulin secretion, may result in significant hypoglycemia Glipizide, glyburide, glucagon,acetohexamide, chlorpropamide, tolazamide, tolbutamide, glimepiride –Α-glucosidase inhibitors - ↓ carb absorption Acarbose, miglitol –Biguanides - ↓ hepatic production and absorption of glucose Metformin (glucophage) –Thiazolidinediones – increase effect of insulin Avandia, actos

39. Common Prescription Medications Insulin –Rapid acting (onset 15 min – 1 hr) Regular, NovolinR, HumulinR, Lispro, Semilente –Intermediate (onset 1 – 2.5 hr) NPH, HumulinN, NovolinN, Lente –Long acting (onset 4 – 8 hr) Ultralente