CLINICAL PATHOPHYSIOLOGY CASE 4

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

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

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

4. PAST MEDICAL HISTORY • None • No medications

5. VITAL SIGNS • Pulse 120 • Respirations 36 • Blood pressure 100/60 • Temperature 980F • Oxygen saturation 100% • Pain: none

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

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

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

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

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

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

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

13. DIAGNOSTIC TESTS • Blood tests • Serum Electrolytes

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 • 540 mg/dL – 100 mg/dL = 440 mg/dL • 1.6 X 4.4 = 7.04 • 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 • pH 7.4 – 7.2 = 0.2 • 0.2 x 0.6 mEq/L = 1.2 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: • pH: 7.20 • PO2: 105 mmHg • PCO2 : 20 mmHg • HCO3-: 12 mEq/L Metabolic Acidosis with Respiratory Compensation

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

18. SERUM OSMOLALITY • Correlates to mental status • Measured by freezing point depression • 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 • Estimated true prevalence: 18.2 million Americans • Annual cost: $132 billion • Initial presentation is diabetic ketoacidosis (DKA) in 10% of cases

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

21. DIABETIC KETOACIDOSIS (DKA)Biochemical Characteristics • Hyperglycemia • Blood sugar > 300 mg/dL • Ketonemia • Serum ketones positive at > 1:2 dilution (sodium nitroprusside test) • Acidosis • pH < 7.30 • HCO3- < 15 mEq/L Hyperglycemia DKA Ketonemia Acidosis

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

23. PATHOPHYSIOLOGY OF DKA

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

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

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

27. PATHOPHYSIOLOGY OF DKA • Hyperglycemia results from: • Blockage of intracellular glucose transport • Counter-regulatory hormone effects

28. Effects of Hyperglycemia in DKA

29. Effects of Hyperglycemia in DKA

30. Effects of Hyperglycemia in DKA

31. PATHOPHYSIOLOGY OF DKA

32. PATHOPHYSIOLOGY OF DKA

33. CLINICAL PRESENTATIONEarly Symptoms • Due to hyperglycemia • Polyuria • Polydipsia • Polyphagia • Visual disturbances • Due to muscle breakdown and dehydration • Weight loss • Weakness

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

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

36. CLINICAL PRESENTATIONLater Symptoms • Due to hypokalemia • Gastric stasis and ileus • Muscle cramps • Cardiac dysrhythmias

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

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

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

40. DKA MANAGEMENT • 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 MANAGEMENTElectrolytes • 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 phosphate • Monitor hourly

42. DKA MANAGEMENTFlow Sheet • Hourly Observations • Electrolytes • Glucose • Osmolality • Blood gases • Output • Vital signs • Mental status

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

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

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

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

47. DKA DISPOSITION • ICU • Age < 2 years or > 60 years • pH < 7.0 • Serious concurrent illness • (Blood sugar > 1000) • 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 is a state of endocrinological imbalance involving insulin AND counter-regulatory hormones • 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 • 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. • Bicarbonate therapy is rarely indicated.