Mixed acid-base disorders

Metabolic acidosis is a primary fall in serum bicarbonate that is first confirmed with an arterial or venous blood gas, then classified by the serum anion gap into an increased anion gap process (unmeasured organic anion, most often lactate) or a normal anion gap process (bicarbonate loss from the gut or kidney). The urine anion gap and clinical context localize the cause, and management targets the underlying disease, reserving intravenous sodium bicarbonate for severe acidemia (pH less than 7.1-7.2) or specific indications such as chronic kidney disease and renal tubular acidosis.

Respiratory acidosis is retention of arterial carbon dioxide from impaired alveolar ventilation, producing hypercapnia and a low pH that is buffered acutely and partially corrected over 3 to 5 days by renal bicarbonate reabsorption. Management corrects the underlying ventilatory mechanism, escalating from treatment of the precipitant to noninvasive and then invasive mechanical ventilation based on the degree of acidosis, mental status, and hemodynamic stability.

Metabolic alkalosis is a primary rise in serum bicarbonate generated by acid loss or alkali retention (usually vomiting, nasogastric suction, or diuretic use) and sustained by a maintenance state, most often volume contraction, hypokalemia, or mineralocorticoid excess. The urine chloride level is the key diagnostic branch point, separating chloride-responsive (saline-responsive) causes, treated with isotonic saline and potassium repletion, from chloride-resistant causes driven by mineralocorticoid excess, treated with potassium repletion and correction of the underlying endocrine or genetic disorder.

Respiratory alkalosis is a reduction in arterial Pco2 from increased alveolar ventilation, most often driven by sepsis, hepatic failure, anxiety, hyperventilation, pregnancy, or salicylate toxicity, presenting with tachypnea, lightheadedness, and paresthesia. Diagnosis rests on arterial blood gas confirmation of a primary fall in Pco2 with the expected compensatory drop in bicarbonate, and management targets the underlying driver rather than the blood gas itself, with acetazolamide or controlled hypoventilation reserved for rare severe alkalemia with hemodynamic compromise.

Lactic acidosis is a high anion gap metabolic acidosis from a serum lactate above 4.0 mmol/L, most often type A from tissue hypoperfusion (septic, cardiogenic, or hypovolemic shock) or type B from impaired metabolism (metformin, mitochondrial toxins, malignancy). Diagnosis rests on the anion gap plus lactate level; management treats the underlying cause, since bicarbonate is reserved for arterial pH below 7.1-7.15.

Diabetic ketoacidosis is a life-threatening hyperglycemic crisis of near-absolute insulin deficiency, most common in type 1 diabetes, producing an anion-gap ketoacidosis from unrestrained lipolysis and osmotic diuresis from severe hyperglycemia. It is diagnosed by hyperglycemia, ketonemia, and an anion-gap metabolic acidosis, and treated with intravenous isotonic saline, an intravenous regular insulin bolus and infusion, and aggressive potassium repletion guided by frequent electrolyte monitoring.

Renal tubular acidosis is a normal anion gap metabolic acidosis caused by impaired renal bicarbonate reabsorption (type 2, proximal) or impaired distal acid excretion (type 1, hypokalemic distal, or type 4, hyperkalemic distal from aldosterone deficiency or resistance). The urine anion gap, serum potassium, and urine pH distinguish the three types, which are treated respectively with alkali replacement plus a thiazide, potassium citrate, and correction of the underlying cause plus mineralocorticoid replacement when appropriate.

Chronic kidney disease is abnormal kidney structure or function present for more than 3 months, staged by the Kidney Disease: Improving Global Outcomes (KDIGO) system using estimated glomerular filtration rate and albuminuria, and managed with blood pressure control, renin-angiotensin blockade, an SGLT2 inhibitor, and correction of its metabolic complications.

Acute kidney injury is a sudden rise in serum creatinine or fall in urine output from prerenal, intrinsic, or postrenal causes, defined and staged by KDIGO criteria. Management targets the underlying cause, corrects volume and electrolyte derangements, and escalates to renal replacement therapy for refractory hyperkalemia, acidosis, volume overload, or uremia.

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, identified by an acute rise in SOFA score of 2 points or more in a patient with known or suspected infection. Survival depends on recognizing the pattern early and completing the hour-1 bundle: lactate, blood cultures before antibiotics, broad-spectrum antibiotics such as cefepime 2 g IV every 8 hours, and 30 mL/kg crystalloid for hypotension or a lactate of 4 mmol/L or higher.

Septic shock is the subset of sepsis with hypotension requiring vasopressors to maintain a mean arterial pressure above 65 mm Hg plus a serum lactate above 2 mmol/L despite adequate fluid resuscitation, carrying in-hospital mortality of 40% or higher. Management is a timed sequence: 30 mL/kg crystalloid bolus, blood cultures and broad-spectrum antibiotics within 1 hour, norepinephrine titrated to MAP >=65, and escalation to a second vasopressor and stress-dose hydrocortisone when hypotension persists.

Cirrhosis is end-stage hepatic fibrosis with regenerative nodules, staged as compensated or decompensated by the onset of ascites, variceal hemorrhage, encephalopathy, or jaundice. Severity is graded by Child-Pugh class and MELD, and management centers on treating the underlying cause, surveillance for varices and hepatocellular carcinoma, and timely transplant referral once decompensation appears.

Heart failure is a clinical syndrome of impaired cardiac filling or ejection causing congestion and reduced perfusion, classified by ejection fraction. Diagnosis integrates symptoms, signs, natriuretic peptides, and echocardiography, and treatment of reduced-ejection-fraction disease is quadruple guideline-directed therapy, with device therapy and cause-specific management.

Hypokalemia is a serum potassium level below 3.5 mEq/L, most often caused by gastrointestinal or renal potassium losses, and it produces weakness, ileus, and arrhythmia risk through altered membrane excitability. Diagnosis rests on the urine potassium-creatinine ratio to separate renal from extrarenal causes, and treatment is intravenous or oral potassium chloride, with concurrent magnesium repletion, dosed to severity and symptoms.

Hyperkalemia is a serum potassium level above 5.0 mEq/L, most often from decreased kidney excretion, transcellular shifts, or excess intake, with levels above 6.0-6.5 mEq/L or any ECG change constituting a medical emergency from the risk of fatal arrhythmia. Treatment sequences cardiac membrane stabilization with calcium, transcellular potassium shifting with insulin/dextrose and albuterol, then definitive potassium removal with binders, diuretics, or dialysis.

Primary hyperaldosteronism is autonomous adrenal aldosterone secretion that suppresses renin, producing hypertension with or without hypokalemia and metabolic alkalosis. It is screened with a plasma aldosterone-to-renin ratio and confirmed with a saline infusion or oral sodium loading test. Unilateral adenomas are treated with laparoscopic adrenalectomy, while bilateral hyperplasia is treated with a mineralocorticoid receptor antagonist such as spironolactone.

Diarrhea is three or more unformed stools daily, split by duration into acute (under 14 days, usually infectious), persistent (14 to 30 days, often parasitic), and chronic (over 30 days, usually noninfectious), and by mechanism into osmotic, secretory, inflammatory, malabsorptive, and motility diarrhea. Acute diarrhea is managed with rehydration and tested only when red-flag features are present, while chronic diarrhea is worked up by mechanism using stool studies, celiac serology, fecal calprotectin, and endoscopy.