CASE #7

A 35 year old male has been an insulin requiring diabetic since age 10. He was poorly compliant as a teenager and was hospitalized several times with diabetic ketoacidosis. Over the past 10 years he has been very casual about following dietary instructions and the prescribed insulin dosing. Proteinuria was first detected at age 28 and increase in serum creatinine to 2.5 was found at age 32. Hypertension was noted at the time and he was started on a combination diuretic of hydrochlorothiazide with spironolactone. He continued to obtain refills of his diuretic and insulin by phone but failed to keep appointments with his physician.

Because of headaches and malaise he finally saw his physician.

Physical Examination: showed an anxious male. BP 190/110; ankles showed 2+ edema.

The physician prescribed enalapril (angiotensin-converting enzyme inhibitor) and increased the dose of the combination diuretic to twice daily. He also sent the patient to a laboratory for blood tests. Two days later, about two hours after taking his medication, the patient became progressively weaker and then noted severe lightheadedness on standing. He was taken to an emergency room. There blood pressure was found to be 85/50. Blood was sent for electrolytes and an EKG showed the following pattern: [EKG]

1. Using the serum and urine data, determine the cause of the patient's acidemia. What is the mechanism of the acidemia?

Non-gap metabolic acidosis, (AG =10); appropriate compensation;

Urine AG = 30 + 15 - 35 = +10: This suggests inadequate ammoniagenesis or decreased proton secretion, i.e. Type I or IV RTA; hyperkalemia suggests Type IV.

Mechanism is suppressed ammonium generation because of hyperkalemia (hyperkalemia is multifactorial - tubular resistance to aldo, low aldo, hyoreninism, etc.)

2. What are the main factors regulating renal potassium excretion by the kidney? In this patient, is the decreased GFR a likely cause of decreased potassium excretion? What other non-pharmacologic factors may be at play here?

a. GFR, Urine flow rate and Na delivery to distal nephron, aldosterone

b. No--usually not a factor until GFR <10 cc/min.

c. see above Type IV RTA discussion, also ¯ insulin, metabolic acidosis, hyperosmolality

3. Which component in the diuretic combination may have played a role in the development of extreme hyperkalemia? How? What would have been a more appropriate diuretic for this patient in terms of both efficacy and different effect on serum potassium?

a. Spironolactone inhibited aldosterone (discuss mechanism)

b. Furosemide preferred: loop diuretic more potent diuretic and causes kaluresis.

4. Describe the effects of enalopril on hormonal pathways which could ahve reduced the renal excretion of potassium.

ACE inhibitor reduces ATII and aldosterone, inhibiting K excretion.

Lab data drawn two months earlier showed: K 5.3, BUN 102, Creatine 8.3.

5. How would you treat this patient's hyperkalemia?

Emergent: CaCl2 or Ca gluconate IV (onset 0-5 min)

• mechanism--membrane stabilization, no effect on K distribution

Insulin/Glucose (onset 15-60 min)

• these redistribute, but do not rid body of excess K

6. In milder hyperkalemia the EKG appearance would be as shown. Discuss the main abnormality. [EKG: Peaked T Waves]