Metabolic (including renal) Acid-Base Imbalance

1. Metabolic Acidosis shows bicarbonate depletion
   • Retention of protons or loss of bicarbonate (bicarb < 24)

     Metabolic acidosis may be produced by any disorder (inside or outside the kidney) that affects H+ or bicarbonate concentration.

   • Pulmonary compensation (rapid and robust)

     In contrast to renal compensation for respiratory acid-base problems (which develops slowly), the lung can respond rapidly to pH imbalances by altering the respiratory rate. Thus respiratory compensation for metabolic acidosis in patients with normal lungs develops quickly.

   • Increased "anion gap" in metabolic acidosis

     The "Anion Gap" is the difference between the sum of the cations and the sum of the anions measured in a standard electrolyte test panel (i.e., sodium and potassium vs. chloride and bicarbonate--also see note below). The rest of the ions in plasma are referred to as "unmeasured", though many of them could be measured through specific tests if necessary. The "unmeasured anions" include proteins (most of which have a net negative charge and are thus anionic) and a variety of waste products and other anions such as sulfate, phosphate, ketoacids, lactic acid, etc.

     In the animated anion gap diagram, the cation and anion bars must maintain equal height (negative and positive charges must balance). An increase in "unmeasured anions" is balanced either by a decrease in chloride and/or bicarbonate (if the cations stay the same) or by an increase in sodium. In either case, the difference between (Na + K) and (Cl + bicarb) will increase. This occurs in renal failure where excretion "unmeasured anions" decreases, or in diabetic ketoacidosis, where ketoacid production increases. Both of these are examples of metabolic acidosis with increased anion gap.

     In situations where acidosis is caused by bicarbonate depletion (renal tubular dysfunction affecting carbonic anhydrase or protracted diarrhea with loss of pancreatic bicarbonate), sodium will be lost to balance the loss of bicarbonate and thus the difference in (Na + K) vs. (Cl + bicarb) with not change substantially.

     Note: Various authorities calculate the anion gap in slightly different ways. Some use the difference between the sum of sodium and potassium and the sum of chloride and bicarbonate [(Na + K) - (Cl + bicarb)], as above. Others recognize that potassium is fixed within relatively narrow limits, so it works just as well to subtract the sum of chloride and bicarbonate from sodium alone [Na - (Cl + bicarb)] and compare the result to slightly lower reference values. Either way is fine as long as you use the correct reference values for comparison (Don't worry about learning reference values except in general terms--they are often site-specific and will usually be supplied for you when you need to interpret data).

   • Causes
     • Anion Gap
       • Renal failure
       • Ketosis
       • Lactic acidosis
       • Poisoning

     • Non-Anion Gap
       • Renal tubular dysfunction (Fanconi's syndrome)

         Fanconi's syndrome is an inherited or acquired disorder that affects multiple proximal tubular processes, including carbonic anhydrase and glucose/amino acid uptake. These patients exhibit a variety of findings including glycosuria and amino aciduria in addition to acidosis.

       • Diarrhea (loss of pancreatic bicarbonate that is normally secreted into the small intestine)

2. Metabolic alkalosis shows bicarbonate excess
   • Loss of acid or retention of bicarbonate

   • Pulmonary compensation (rapid but limited)

     Although the lung can respond rapidly to alkalosis, it has a limited ability to retain carbon dioxide (and thus acid) by decreasing the breathing rate because oxygenation of the blood can't be compromised. In general, the homeostatic mechanisms in the body are designed with a much greater capacity to resist acidosis than alkalosis. This is because the major problem in pH balance normally is the removal of acid produced in metabolism.

   • Causes
     • Vomiting (loss of gastric acid)
     • Diuretics (renal loss of potassium and acid in the distal tubule)
     • Elevated corticosteroids (Cushing's syndrome and hyperaldosteronism; renal loss of potassium and acid in the distal tubule)
     • Severe potassium depletion

       Requires sodium uptake in the distal tubule to balance by secreting protons and also causes protons to be taken up into cells in exchange for intracellular potassium that leaks out of cells down the increased concentration gradient.

     • Acute alkalai ingestion