1. Mara Nitu, MD* 2. Greg Montgomery, MD† 3. Howard Eigen, MD§ 1. *Associate Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy; Medical Director, PICU/Riley Hospital for Children; Medical Co-Director of Lifeline Transport Team, Indianapolis, IN. 2. †Assistant Professor of Clinical Pediatrics, Section of Pulmonology, Critical Care and Allergy; Medical Director, Pediatric Bronchoscopy Laboratory, James Whitcomb Riley Hospital for Children, Indianapolis, IN. 3. §Billie Lou Wood Professor of Pediatrics, Associate Chairman for Clinical Affairs; Director, Section of Pediatric Pulmonology, Critical Care and Allergy, James Whitcomb Riley Hospital for Children, Indianapolis, IN. After completing this article, readers should be able to: 1. Understand the mechanisms for regulating acid-base physiology. 2. Know the differential diagnosis of metabolic acidosis associated with high anion gap and plan for initial management. 3. Know the differential diagnosis of normal anion gap metabolic acidosis. 4. Describe pulmonary compensatory changes in metabolic acidosis and alkalosis. 5. Understand how various diuretics can lead to acid-base imbalance. 6. Describe renal compensatory changes in respiratory acidosis and alkalosis. A 16-year-old girl who has no significant previous medical history presents to the emergency department with a 4-day history of nausea, vomiting, fever, chills, diarrhea, leg cramps, abdominal pain, and headaches. She is finishing her menstrual period and arrives with a tampon in place, which she reports that she inserted yesterday. Her vital signs include a heart rate of 165 beats/min, respiratory rate of 28 breaths/min, blood pressure 65/30 mm Hg, and oxygen saturation of 100% on 4 L/min of oxygen. The most likely diagnosis for this patient is toxic shock syndrome, which was later confirmed with a positive antibody test. The initial arterial blood gas (ABG) values are: Such findings are suggestive of metabolic acidosis with respiratory compensation. Further laboratory results are: