1. CLINICAL PATHOPHYSIOLOGY CASE 4 Janet Lin, MD, MPH Assistant Professor Department of Emergency Medicine

2. Emergency Department Presentation 22 y.o. female 22 y.o. female Vomiting Vomiting –Multiple episodes –2 days duration Lethargic, but arousable Lethargic, but arousable Abdominal pain Abdominal pain –Generalized

3. HISTORY OF PRESENT ILLNESS No fever No fever No chills No chills No prior similar episodes No prior similar episodes Other Other

4. PAST MEDICAL HISTORY None None No medications No medications

5. VITAL SIGNS Pulse 120 Pulse 120 Respirations 36 Respirations 36 Blood pressure 100/60 Blood pressure 100/60 Temperature 98 0 F Temperature 98 0 F Oxygen saturation 100% Oxygen saturation 100% Pain: none Pain: none

6. PHYSICAL EXAMINATION Skin: pale & dry Skin: pale & dry Mucous membranes: dry & cracked Mucous membranes: dry & cracked Heart: normal with tachycardia Heart: normal with tachycardia Lungs: clear with tachypnea Lungs: clear with tachypnea

7. PHYSICAL EXAMINATION Abdomen: soft, minimally tender Abdomen: soft, minimally tender Neuro: no focal findings Neuro: no focal findings No evidence of trauma No evidence of trauma Conclusions?

8. DIFFERENTIAL DIAGNOSIS 1. 1. 2. 2. 3. 3. 4. 4. 5. 5. 6. 6.

9. DIAGNOSTIC TESTS Blood tests Blood tests Urine tests Urine tests Radiology tests Radiology tests Special tests Special tests Why is each test ordered?

10. BEDSIDE GLUCOSE TESTING Glucose oxidase reagent strip Glucose oxidase reagent strip Light meter increases sensitivity Light meter increases sensitivity Sensitive to light, heat, moisture Sensitive to light, heat, moisture More accurate in the low range More accurate in the low range Accucheck: 180-240 mg/dL

11. DIAGNOSTIC TESTS Electrocardiogram (ECG) Normal sinus rhythm Normal sinus rhythm Normal T-waves Normal T-waves No ST changes No ST changes Look for evidence of hyperkalemia!

12. BEDSIDE DIAGNOSTIC TESTS Urine glucose and acetone Urine glucose and acetone –Clinitest –Acetest –Chemstrips bG Glucose: 4+ Ketones: 2+

13. DIAGNOSTIC TESTS Blood tests Blood tests –Serum Electrolytes NaClBUN Glu K CO 2 Cr 130100305404.0121.8

14. CORRECTION FOR SERUM SODIUM The sodium level is reduced by 1.6 mEq/L for every 100 mg/dL the glucose level is over 100 mg/dL The sodium level is reduced by 1.6 mEq/L for every 100 mg/dL the glucose level is over 100 mg/dL 540 mg/dL – 100 mg/dL = 440 mg/dL 540 mg/dL – 100 mg/dL = 440 mg/dL 1.6 X 4.4 = 7.04 1.6 X 4.4 = 7.04 Corrected Sodium = 130 +7 = 137 mEq/L Corrected Sodium = 130 +7 = 137 mEq/L

15. Estimation of Serum Potassium if pH were Normal Serum potassium will fall by 0.6 mEq/L for each 0.1 increase in pH Serum potassium will fall by 0.6 mEq/L for each 0.1 increase in pH pH 7.4 – 7.2 = 0.2 pH 7.4 – 7.2 = 0.2 0.2 x 0.6 mEq/L = 1.2 mEq/L 0.2 x 0.6 mEq/L = 1.2 mEq/L 4.0 mEq/L – 1.2 mEq/L = 2.8 mEq/L 4.0 mEq/L – 1.2 mEq/L = 2.8 mEq/L –The expected serum potassium level when pH is corrected will be dangerously low

16. DIAGNOSTIC TESTS Arterial blood gases: Arterial blood gases: –pH: 7.20 –PO 2 : 105 mmHg –PCO 2 : 20 mmHg –HCO 3 - : 12 mEq/L Metabolic Acidosis with Respiratory Compensation

17. DIAGNOSTIC TESTS Serum acetone: + @ 1:8 dilution Serum acetone: + @ 1:8 dilution

18. SERUM OSMOLALITY Correlates to mental status Correlates to mental status Measured by freezing point depression Measured by freezing point depression Calculated from clinical chemistries Calculated from clinical chemistries –OSM = 2(Na) + Glu/18 + BUN/3 –OSM = 2(130) + 540/18 + 30/3 –OSM = 300 mOSM/L –Normal OSM = 285 – 295 mOSM/L

19. DIABETES MELLITUS First described in Egypt 3000 years ago First described in Egypt 3000 years ago Estimated true prevalence: 18.2 million Americans Estimated true prevalence: 18.2 million Americans Annual cost: $132 billion Annual cost: $132 billion Initial presentation is diabetic ketoacidosis (DKA) in 10% of cases Initial presentation is diabetic ketoacidosis (DKA) in 10% of cases

20. DIABETIC KETOACIDOSIS (DKA) State of endocrinologic imbalance State of endocrinologic imbalance –Insulin deficiency –Counter-regulatory hormone excess

21. DIABETIC KETOACIDOSIS (DKA) Biochemical Characteristics Hyperglycemia Hyperglycemia –Blood sugar > 300 mg/dL Ketonemia Ketonemia –Serum ketones positive at > 1:2 dilution (sodium nitroprusside test) Acidosis Acidosis –pH < 7.30 –HCO 3 - < 15 mEq/L Hyperglycemia Acidosis Ketonemia DKA

22. Factors Predisposing to the Development of DKA Lack of adequate knowledge of the disease (2/3) Lack of adequate knowledge of the disease (2/3) Psychological problems Psychological problems Financial difficulties Financial difficulties Intercurrent illness (> 80%) Intercurrent illness (> 80%) –Infection (30-40%) –Vomiting –Myocardial infarction –CVA –Pregnancy –Other stressors

23. PATHOPHYSIOLOGY OF DKA DKA COUNTER- REGULATORY HORMONE EXCESS INSULIN DEFICIENCY

24. Relative or absolute Relative or absolute Prevents glucose from entering cells Prevents glucose from entering cells Intracellular “starvation” Intracellular “starvation”

25. COUNTER-REGULATORY HORMONES Stress and intracellular starvation cause release of: Stress and intracellular starvation cause release of: –Catecholamines –Glucagon –Cortisol –Growth hormone

26. COUNTER-REGULATORY HORMONE EFFECTS Gluconeogenesis Gluconeogenesis Breakdown of proteins and conversion of amino acids into glucose Breakdown of proteins and conversion of amino acids into glucose Glycogenolysis Glycogenolysis Breakdown of liver glycogen into glucose Breakdown of liver glycogen into glucose Lipolysis Lipolysis Breakdown of adipose tissue into non-esterified fatty acids (NEFA) Breakdown of adipose tissue into non-esterified fatty acids (NEFA)

27. PATHOPHYSIOLOGY OF DKA Hyperglycemia results from: Hyperglycemia results from: –Blockage of intracellular glucose transport –Counter-regulatory hormone effects Insulin Deficiency Hyperglycemia CRH Excess

28. Effects of Hyperglycemia in DKA HYPERGLYCEMIA HYPEROSMOLARITY Mental Status Changes GLUCOSURIA

29. Effects of Hyperglycemia in DKA GLUCOSURIA OSMOTIC DIURESIS DEHYDRATION

30. Effects of Hyperglycemia in DKA KETOACIDS HYDROGEN IONS ACIDOSIS

31. PATHOPHYSIOLOGY OF DKA ELECTROLYTE IMBALANCE ACIDOSISDEHYDRATION DIAPHORESISTACHYPNEA

32. PATHOPHYSIOLOGY OF DKA DEHYDRATION SHOCK INCREASED ACIDOSIS DECREASED GFR ACUTE TUBULAR NECROSIS INCREASED HYPERGLYCEMIA

33. CLINICAL PRESENTATION Early Symptoms Due to hyperglycemia Due to hyperglycemia –Polyuria –Polydipsia –Polyphagia –Visual disturbances Due to muscle breakdown and dehydration Due to muscle breakdown and dehydration –Weight loss –Weakness

34. CLINICAL PRESENTATION Later Symptoms Due to ketonemia Due to ketonemia –Anorexia –Nausea –Vomiting –Fruity acetone breath Due to acidosis Due to acidosis –Abdominal pain –Kussmaul respirations (deep, regular, sighing)

35. CLINICAL PRESENTATION Later Symptoms Due to hyperosmolarity Due to hyperosmolarity –Altered level of consciousness Alert patients have OSM < 330 mOSM/kg Alert patients have OSM < 330 mOSM/kg 20% of patients are alert 20% of patients are alert 10% of patients are comatose 10% of patients are comatose

36. CLINICAL PRESENTATION Later Symptoms Due to hypokalemia Due to hypokalemia –Gastric stasis and ileus –Muscle cramps –Cardiac dysrhythmias

37. CLINICAL PRESENTATION DKA Pearls Vague symptoms Vague symptoms Hyperpyrexia rare Hyperpyrexia rare Severe in cases in those who cannot communicate Severe in cases in those who cannot communicate Signs & Symptoms ≠ Biochemical Abnormality Signs & Symptoms ≠ Biochemical Abnormality Dehydrated patient who is still voiding = DKA Dehydrated patient who is still voiding = DKA

38. DIABETIC KETOACIDOSIS Differential Diagnosis Hypoglycemia Hypoglycemia Meningitis Meningitis Acute abdomen Acute abdomen Gastroenteritis Gastroenteritis Respiratory infection Respiratory infection Toxic ingestion Toxic ingestion CVA CVA Brainstem hemorrhage Brainstem hemorrhage Uremia Uremia Alcoholic ketoacidosis Alcoholic ketoacidosis Starvation ketosis Starvation ketosis

39. DKA MANAGEMENT INTRAVENOUS FLUID ADMINISTRATION INTRAVENOUS FLUID ADMINISTRATION INSULIN THERAPY INSULIN THERAPY ELECTROLYTES ELECTROLYTES MONITOR USING A FLOW SHEET MONITOR USING A FLOW SHEET (BICARBONATE THERAPY) (BICARBONATE THERAPY)

40. DKA MANAGEMENT INTRAVENOUS FLUID ADMINISTRATION INTRAVENOUS FLUID ADMINISTRATION –Lowers blood glucose by as much as 18% –Normalizes pH –Normal saline, 1 L over 30 min –Then, Normal saline, 1 L over 1-2 h –Then, 0.5 NS @ 300-500 mL/h, guided by urine output

41. DKA MANAGEMENT Electrolytes Potassium Potassium –Level will fall precipitously with treatment –Hold only if peaked T-waves on ECG –20-40 mEq in the first liter of fluid ½ as chloride ½ as chloride ½ as phosphate ½ as phosphate –Monitor hourly

42. DKA MANAGEMENT Flow Sheet Hourly Observations Hourly Observations –Electrolytes –Glucose –Osmolality –Blood gases –Output –Vital signs –Mental status

43. DKA MANAGEMENT Insulin Therapy Route of Administration Route of Administration –IM: delayed absorption –SQ High doses High doses Rapid fluctuations Rapid fluctuations –IV continuous infusion Low dose Low dose Linear decline Linear decline Less hypoglycemia Less hypoglycemia Less hypokalemia Less hypokalemia Adjustments easy Adjustments easy

44. DKA MANAGEMENT Insulin Therapy IV continuous infusion IV continuous infusion 0.1 unit/kg/h 0.1 unit/kg/h Loading dose of 0.1 unit/kg used by some Loading dose of 0.1 unit/kg used by some For BS>1000; 0.05 units/kg/h For BS>1000; 0.05 units/kg/h When BS reaches 300, reduce to 0.05 units/kg/h & add glucose to the fluid When BS reaches 300, reduce to 0.05 units/kg/h & add glucose to the fluid Continue until acidosis corrected, BS controlled & ketonemia resolved. Continue until acidosis corrected, BS controlled & ketonemia resolved.

45. DKA MANAGEMENT Bicarbonate Therapy Complications Complications –Shift of oxyhemoglobin dissociation curve to the left –Hypokalemia & hypomagnesemia –Overcorrection alkalosis –Paradoxical CSF acidosis –Cerebral edema Evidence for effectiveness: lacking Evidence for effectiveness: lacking

46. DKA MANAGEMENT Bicarbonate Therapy Consider only if pH < 7.0 Consider only if pH < 7.0 If used, DO NOT PUSH! If used, DO NOT PUSH! –Administer as 1-2 mEq/kg over 2 h

47. DKA DISPOSITION ICU ICU –Age 60 years –pH < 7.0 –Serious concurrent illness –(Blood sugar > 1000) Outpatient Management Outpatient Management –Alert –No persistent vomiting –Mild acidosis, ketonemia & dehydration

48. DKA SUMMARY DKA may be the presenting complaint in new diabetics, up to 10% of the time DKA may be the presenting complaint in new diabetics, up to 10% of the time DKA is a state of endocrinological imbalance involving insulin AND counter- regulatory hormones DKA is a state of endocrinological imbalance involving insulin AND counter- regulatory hormones DKA is characterized by the presence of hyperglycemia, acidosis and ketonemia. DKA is characterized by the presence of hyperglycemia, acidosis and ketonemia.

49. DKA SUMMARY Laboratory evaluation of the DKA patient is complex and must be repeated on an hourly basis until the patient is stable Laboratory evaluation of the DKA patient is complex and must be repeated on an hourly basis until the patient is stable The most important components of the management of the DKA patient are fluid and electrolyte management. The most important components of the management of the DKA patient are fluid and electrolyte management. Insulin is an essential but secondary component of management. Insulin is an essential but secondary component of management. Bicarbonate therapy is rarely indicated. Bicarbonate therapy is rarely indicated.