Renal function, electrolytes, and acid-base balance

Kidney chemistry and acid-base balance look intimidating because they mix numbers, physiology, and a little arithmetic. The board rewards you for handling all three calmly. Once you know what urea and creatinine each tell you, how to compute an anion gap and a creatinine clearance, and how to sort a blood gas into one of four boxes, this whole area becomes a set of short, reliable calculations rather than a memory dump.

Urea, creatinine, and the glomerular filtration rate

The kidney's filtering capacity is the glomerular filtration rate (GFR). Two waste products estimate it.

• Urea (reported in many labs as blood urea nitrogen, BUN) is the end product of protein metabolism. It is filtered but partly reabsorbed, so it rises with dehydration, a high-protein diet, or gastrointestinal bleeding even when the kidney is fine.
• Creatinine is a waste product of muscle creatine, produced at a fairly constant rate and freely filtered with little reabsorption. That steadiness makes creatinine the better single marker of GFR.

The BUN to creatinine ratio adds information. A high ratio with otherwise normal kidneys suggests a prerenal problem such as dehydration, where urea is reabsorbed with water while creatinine is not.

Worked example: creatinine clearance two ways

The measured creatinine clearance uses a timed urine:

Clearance = (U × V) / P

where U is urine creatinine, P is plasma creatinine (same units), and V is urine flow in mL/min. If U is 120 mg/dL, P is 1.0 mg/dL, and V is 1.0 mL/min, then clearance = (120 × 1.0) / 1.0 = 120 mL/min.

The estimated clearance uses the Cockcroft-Gault formula:

Clearance = [(140 − age) × weight in kg] / (72 × serum creatinine in mg/dL), multiplied by 0.85 for a woman.

For a 60-year-old man weighing 70 kg with a serum creatinine of 1.0 mg/dL: (140 − 60) × 70 = 5600, divided by (72 × 1.0) = 72, giving about 78 mL/min. Note that clearance falls as age rises and as serum creatinine rises.

Uric acid

Uric acid is the end product of purine (nucleic acid) metabolism. High levels cause gout when urate crystals deposit in joints, and they spike in tumor lysis syndrome when many cells break down at once during chemotherapy. It is a durable, high-yield fact that uric acid comes from purines, not proteins.

The major electrolytes

Four electrolytes carry most of the exam weight.

• Sodium (Na) is the main extracellular cation and the chief driver of plasma osmolality and water balance.
• Potassium (K) is the main intracellular cation. Because so little is outside the cells, small shifts change the serum value fast, and both high and low potassium disturb cardiac rhythm. A key preanalytic trap: hemolysis falsely raises potassium as it leaks from ruptured red cells, and letting a tube sit or clenching the fist during the draw can do the same.
• Chloride (Cl) follows sodium and helps maintain electrical neutrality.
• Bicarbonate (HCO3) is the main buffer base and the metabolic side of acid-base balance.

The anion gap

The anion gap flags unmeasured acids:

Anion gap = Na − (Cl + HCO3)

A widened gap means unmeasured acids are present. Suppose Na is 140, Cl is 104, and HCO3 is 16 mmol/L. Then anion gap = 140 − (104 + 16) = 140 − 120 = 20 mmol/L, which is high. High-anion-gap metabolic acidosis comes from added acids: lactic acidosis, ketoacidosis, kidney failure (uremia), and toxins such as methanol or ethylene glycol. A normal anion gap acidosis (hyperchloremic) comes from bicarbonate loss, as in diarrhea.

Reading a blood gas: the four disorders

Three numbers do the work: pH (about 7.35 to 7.45), pCO2 (the respiratory component), and HCO3 (the metabolic component). Work in two steps.

Step 1: Is the pH acidic or alkaline? Below 7.35 is acidemia; above 7.45 is alkalemia.

Step 2: Which component matches the pH? A change in pCO2 that explains the pH is respiratory; a change in HCO3 that explains it is metabolic.

Disorder	pH	Primary change
Respiratory acidosis	Low	pCO2 high (retained CO2)
Respiratory alkalosis	High	pCO2 low (hyperventilation)
Metabolic acidosis	Low	HCO3 low
Metabolic alkalosis	High	HCO3 high

Remember the direction rule: for respiratory problems, pH and pCO2 move in opposite directions; for metabolic problems, pH and HCO3 move in the same direction. Compensation is the other system trying to pull the pH back toward normal (for example, fast breathing to blow off CO2 in a metabolic acidosis), but compensation rarely fully corrects the pH.

Worked example: interpret a gas

A patient has pH 7.30, pCO2 30 mmHg, and HCO3 15 mmol/L. The pH is low (acidemia). The HCO3 is low, which matches an acidosis, so the primary problem is a metabolic acidosis. The pCO2 is also low, moving opposite to what a respiratory cause would need, so it represents respiratory compensation (blowing off CO2). That is why you always check both components, not just one.

Specimen notes that change the answer

• Draw a blood gas anaerobically and analyze it promptly (or keep it cold), because exposure to air and delay shift pCO2 and pH.
• Never report potassium from a hemolyzed sample; the falsely high value can look like a dangerous hyperkalemia.
• For electrolytes, prolonged tourniquet time and fist clenching can raise potassium spuriously.

Common traps

• Trusting urea over creatinine as the GFR marker. Creatinine is steadier; urea swings with diet and hydration.
• Reporting a high potassium from a hemolyzed tube instead of recognizing the artifact.
• Forgetting that clearance falls as serum creatinine rises, so a higher creatinine means a lower clearance.
• Mixing up the direction rules: respiratory means pH and pCO2 move opposite; metabolic means pH and HCO3 move together.
• Assuming uric acid comes from protein. It is the end product of purine metabolism.
• Calling a normal-gap acidosis a high-gap one; diarrhea gives a normal gap, added acids give a high gap.

Recap

Creatinine beats urea as a GFR marker, and clearance is (U × V) / P from a timed urine or the Cockcroft-Gault estimate, which drops with age and rising creatinine. Uric acid is the purine end product behind gout. Sodium rules extracellular water, potassium is intracellular and hemolysis-sensitive, and the anion gap, Na minus Cl plus HCO3, separates added-acid acidoses from bicarbonate-loss ones. Read a gas in two steps: acid or alkaline, then match pCO2 (respiratory, opposite direction) or HCO3 (metabolic, same direction), and watch for the partner system compensating.