This document provides an overview of acid-base disorders and the approach to interpreting arterial blood gases (ABGs). It begins with a brief preview of the summary and includes expected changes in different acid-base disorders. The document then presents two medical cases involving patients with acid-base abnormalities. It analyzes the lab results and clinical picture for each case and discusses the diagnoses and treatment. Additional topics covered include causes of metabolic alkalosis and acidosis, interpreting urine and serum electrolytes, and the use of diagnostic tests. The document concludes with a quiz case involving a patient with asthma and theophylline toxicity.

1. ABG series ANAS SAHLE , MD DAMASCUSE HOSPITAL

2. Acid-Base Disorders and the ABG 5

3. BREIF PREVIEW

4. Summary of the Approach to ABGs Check the pH Check the pCO2 Select the appropriate compensation formula Determine if compensation is appropriate Check the anion gap AG=NA – (HCO3 + CL):12±4 If the anion gap is elevated, check the delta-delta G:G Ratio =Δ AG (12-AG) HCO3 (24-HCO3) If a metabolic acidosis is present, check urine pH Generate a differential diagnosis

5. EXPECTED CHANGES IN ACID-BASE DISORDERS From: THE ICU BOOK - 2nd Ed. (1998) [Corrected]

7. HIGH AG M.AC Osmolal gap = measured serum osmolality - (2 NA + gluco8 + bun,8) Corrected osmolal gap = measured serum osmolality - (2 NA + gluco8 + bun,8 + ETOH,6)

8. HIGH AG M.AC High normal

9. Expected PCO2 : Measured PCO2

10. YES NO YES NO YES NO YES NO

11. <5,5 >5,5 Urine AG = (UNA +UK) - UCL

12. METABOLIC ALKALOSIS-2

14. Vomiting

15. Exogenous alkali

16. Hyper- aldosteronism

18. < 20 mEq > 20 mEq HIGH NORMAL

19. Nor decr Yes No nor yes No

20. Case 1 A 43 year-old man with a history of a duodenal ulcer is admitted to the hospital after 3 days of anorexia and vomiting. The physical examination shows mild orthostatic hypotension, flat neck veins, and decreased skin turgor.

21. LAB

22. URINE CL <20

23. CASE 2 A 54 year old Mexican mestizo man was admitted to the Internal Medicine department presenting with altered mental status, paresthesias, hypokalemia, and severe hypertension. The patient worked as a teacher. He was a 10 pack year smoker for 45 years and an occasional drinker. He also has a history of using cocaine and smoking marijuana. He lived a sedentary life, and was obese since childhood, being unable to lose weight with conventional diets. He had no family history of cancer or surgical interventions.

24. CONT- The patient was in good health until three months before admission when he presented with: fatigue, intermittent paresthesias of all limbs, cold intolerance, polyuria, weight gain, and irritability. He consulted a primary care physician that made a diagnosis of diabetes mellitus, hypertension, and dyslipidemia and began treatment with Metformin 850 mg twice daily, Glargine insulin 16 units in the morning, Enalapril 10 mg twice daily, and Atorvastatin 20 mg at night. After one month, the patient discontinued the Enalapril on his own.

25. CONT- During the next few months the patient presented with generalized edema, abdominal striae, and depressive symptoms. Also two days before admission he presented with confusion. On arrival, the physical exam found him to be obese, with plethoric facies, severe edema of the lower limbs, bruising and red-purple abdominal striae. He was confused without any sign of focalization or lateralization.

26. LAB His vital signs showed a blood pressure of 210/140 mmHg, heart rate of 62 beats per minute, respiratory rate of 14 per minute, and temperature of 37.2 degree Celsius. Blood biochemistry results were as follows:

28. Other causes of a low anion gap Increased chloride Hypertriglyceridemia Bromide Iodide Decreased “Unmeasured anions” Albumin Phosphorous IgA Increased “Unmeasured cations” Hyperkalemia Hypercalcemia Hypermagnesemia Lithium Increased cationic paraproteins IgG Chloride Bicarb Sodium Albumin Phos IgA Normal Anion gap Potassium Calcium Magnesium IgG

31. INVESTIGATION: The electrocardiogramshowed a first degree AV block. Thelungs where clear under auscultation. The chest X-ray showed an undefined nodular opacity in the hilar region of the right lung (Figure 2). We started: intravenous administration of large amount of potassium chloride (20 mEq per hour), intravenous insulin, and an intravenous antihypertensive (sodium nitroprusside). Following the treatment he experienced complete remission of mental confusion, and improvement, however his blood pressure did not normalize (150/100 mmHg).

32. INVESTIGATION: . Forty-eight hours later basal plasma renin activity and aldosterone were measured and determined as normal. The respective values were 0.53 ng/ml/h (normal values between 0.2-2.8 ng/ml/h) and 52.5 pg/mL (normal values between 10-160 pg/mL). The abdominal CT scan showed diffuse enlargement of the adrenal glands without focal lesions, without any abnormalities of the liver or spleen (Figure 3).

33. Nor decr Yes No nor yes No

34. INVESTIGATION: The 24 hour free cortisol urinary levels were 6600 μg (normal values 4-100 μg) using the immunoenzymatic method. The ACTH levels were 107 pg/mL (normal values are less than 46 pg/mL), by the quimioluminiscence method. High dose dexamethasone suppression test (8 mg) showed suppression of approximately 8% of the cortisol serum levels. A brain CT scan, including the sellar region was normal.

35. Final Diagnosis On day 24 a CT guided fine-needle lung biopsy was performed, showing histopathological results of a small cell neoplasm.

36. CONTIN: we started ketoconazole 400 mg twice daily with a rapid normalization of blood pressure and potassium plasma levels. Seventy two hours later the patient presented with sepsis due to a right leg cellulitis that was treated with meropenem. Despite a partial response to the medical treatment the patient worsened and developed bilateral pleural effusions, and respiratory failure that required assisted mechanical ventilation dying a few days later.

37. Discussion : The case reported here was presented as a hypertensive crisis associated with hypokalemia, severe metabolic alkalosis and neuropsychiatric symptoms. The rapid deterioration of his health, and some cushingoid characteristics, strongly suggested that the clinical symptoms were secondary to some cause of Cushing's syndrome . Once the blood pressure of the patient decreased, and large amounts of potassium were administrated, a rapid improvement in his neurological status was observed. However, the patient continued to demonstrate minor depressive symptoms (mainly apathy, hypersomnia, irritability, and hopeless thoughts).

38. Discussion : In patients with EAS, psychiatric symptoms are frequently reported in about 50% of cases. The most frequent are depression and psychosis . The elevated levels of ACTH, free urinary cortisol excretion, a positive high dexamethasone suppression test and the hilar opacity observed in chest X-ray strongly suggested that the clinical symptoms were due to a malignant ACTH secreting neoplasm.

39. Discussion The gold standard for the differential diagnosis of pituitary and ectopic ACTH-dependent Cushing's syndrome is the bilateral inferior petrosal sinus sampling after administration of CRH (1 μg/kg). A ratio greater than 3.0 after the administration of CRH is consistent with Cushing's disease. Patients with EAS will have a ratio less than 2 before and after CRH administration because the endogenous hypercortisolism suppresses pituitary ACTH release through negative feedback mechanisms (sensitivity 97%, specificity 100%). High-dose dexamethasone suppression tests have lower sensitivity (81%) and specificity (67%).

40. QUIZE The SCLC is a well recognized origin of EAS. The incidence of SCLC is about 13% of all newly diagnosed lung cancers in Mexico. Ketoconazole has been used to treat Cushing's syndrome by inhibiting adrenal glucocorticoid synthesis. Treatment with ketoconazole promotes a palliative hormonal response in more than 50% of patients. In this patient, ketoconazole (400 mg twice daily) promoted a rapid resolution of hypokalemia and hypertension. Due to a rapid clinical deterioration, the patient was not able to receive standard chemotherapy with carboplatin and etoposide for SCLC.

41. Conclusion EAS requires a well established diagnostic work up, and must be considered strongly in patients with: hypertension . severe hypokalemic metabolic alkalosis. especially when a lung mass is discovered.

43. Medications include metoprolol, colchicine, aspirin and meloxicam.

44. On PE the BP is 130/80, HR 86, RR 16, T 36.1. The heart exam shows an S4 gallop.

46. Which of the following is the most likely cause for the laboratory abnormalities? Increase potassium intake Rhabdomyolysis Distal RTA(4) Adverse effect of meloxicam Adverse effect of colchicine

48. (+)20 URINE AG= K=5,9 <5,5 >5,5 Urine AG = (UNA +UK) - UCL

49. Which of the following is the most likely cause for the laboratory abnormalities? Increase potassium intake Rhabdomyolysis Distal RTA(4) Adverse effect of meloxicam Adverse effect of colchicine

51. Tubulointerstial disease

52. Cyclosporine and tacrolimus

53. Transplant rejection

54. Adrenocorticoid insufficiencyDrugs NSAIDS, Cox 2 inhibitors ACE inhibitors Heparin Beta-blockers Ketoconazole Spironolactone, eplerenone Triamterene, amiloride,trimethoprim, pentamidine Obstructive uropathy* Sickle cell nephropathy* *Probably due to “voltage dependent” type I RTA which has a similar clinical picture (hyperkalemia, non-gap acidosis)

55. Inhibitors of the Renin-Angiotensin-AldosteroneSystem

57. Medications include albuterol, Advair, prednisone and theophylline.

58. He was recently prescribed ciprofloxacin for symptomatic diarrhea after returning home from vacation in Mexico.

59. On exam he is tremulous. BP 110/80.

60. He is in moderate respiratory distress using accessory respiratory muscles.

61. HR is 120 with frequent extra systoles.

62. Lungs show poor air movement and wheezes.

64. Which best describes the acid-base status of this patient? Mixed acute respiratory acidosis with superimposed metabolic alkalosis Mixed metabolic acidosis and chronic respiratory acidosis Acute and chronic respiratory acidosis Mixed respiratory alkalosis and metabolic acidosis

65. QUIZE Theopyliine toxicity: Narrow therapitic range. symptoms Drugs intraction

66. CASE 5 A 55 year old insulin dependent diabetic woman was brought to Casualty by ambulance. She was semi-comatose and had been ill for several days. Past history of left ventricular failure. Current medication was: digoxin. thiazide diuretic.

68. M.ALK

70. Which diagnosis is true? DKA NK-HC LACTIC ACIDOSIS VOMITING IN DKA DIURETIC EFFECT IN DKA

71. Which diagnosis is true? DKA (urine.serumketones?,coma?) NK-HC ( high AG M.AC ?) LACTIC ACIDOSIS (blood pressure?) VOMITING IN DKA (urine CL?) DIURETIC EFFECT IN DKA (urine CL?)

72. NEXT LECTURE Respiratory disorders Cases