L10 (P1) - Acid-Base Disorders

What is metabolic acidosis, and how is it different from acidemia?

Metabolic acidosis is a process involving ↑ H+ and/or ↓ HCO3−. Acidemia is the end result of blood pH <7.35. Metabolic acidosis, respiratory acidosis, or both can cause acidemia.

What do the two sides of CO2 + H2O ⇌ H2CO3 ⇌ HCO3− + H+ represent?

Left side = respiratory/lungs because the lungs regulate CO2. Right side = metabolic/renal because the kidneys regulate HCO3− and H+.

What are the major mechanisms that cause metabolic acidosis?

↑ acid generation, ↓ acid elimination, or loss of HCO3−.

How can diabetes cause metabolic acidosis?

Diabetic ketoacidosis (DKA) causes increased production of ketone acids, increasing H+ and producing high-anion-gap metabolic acidosis.

How can chronic acetaminophen ingestion and metformin contribute to metabolic acidosis?

Chronic acetaminophen ingestion can contribute to accumulation of organic acids; metformin can contribute to lactic acidosis.

How does diarrhea cause metabolic acidosis?

Diarrhea causes GI loss of HCO3− → ↓ serum HCO3− → metabolic acidosis.

Which antibiotic from the lecture is particularly associated with diarrhea that could lead to metabolic acidosis?

Augmentin (amoxicillin/clavulanate).

What are the normal acid-base functions of the proximal renal tubule?

It secretes H+ from the blood into the tubule for elimination and reabsorbs HCO3− back into the bloodstream.

How can Fanconi syndrome or another proximal tubular defect cause metabolic acidosis?

Impaired proximal tubular HCO3− reabsorption → excessive urinary HCO3− loss → metabolic acidosis.

What is the standard serum anion gap equation and normal range?

AG = Na+ − (Cl− + HCO3−). Normal AG is typically 12 ± 4 mEq/L, although the normal range can vary by laboratory.

Why are Na+, Cl−, and HCO3− used in the standard anion gap equation?

Na+ is the major extracellular cation; Cl− and HCO3− are major measured extracellular anions.

Why is K+ commonly excluded from the anion gap equation, and what is the equation if it is included?

K+ is primarily intracellular and has a relatively low extracellular concentration. If included: AG = (Na+ + K+) − (Cl− + HCO3−).

What is another way to conceptualize the anion gap?

AG = all unmeasured anions − all unmeasured cations.

What are important examples of unmeasured anions?

Albumin, lactic acid/lactate, ketone ions, and dihydrogen phosphate (H2PO4−).

What are important examples of unmeasured cations?

Ca2+, Mg2+, iron, zinc, copper, selenium, and positively charged neurotransmitters such as dopamine and serotonin.

How do changes in unmeasured ions affect the anion gap?

↑ unmeasured anions → ↑ AG; ↑ unmeasured cations → ↓ AG; ↓ unmeasured anions → ↓ AG.

Why is albumin important when interpreting the anion gap?

Albumin is a major unmeasured anion. Hypoalbuminemia lowers the measured AG and can mask an otherwise elevated anion gap.

What happens to the anion gap when lactic acid or ketones accumulate?

AG increases because lactate and ketones are unmeasured anions.

What is metabolic alkalosis?

A primary acid-base disorder involving ↓ H+ and/or ↑ HCO3−, resulting in an increased tendency for blood pH to rise.

What are the major contributors to metabolic alkalosis?

Intracellular H+ shift, GI H+ loss (usually vomiting), administration/retention of HCO3−, hyperaldosteronism, drug-induced increases in HCO3−, and impaired renal elimination of HCO3−.

How does vomiting cause metabolic alkalosis?

Vomiting causes GI loss of H+ → ↓ H+ in the body → metabolic alkalosis.

How can decreased kidney function contribute to metabolic alkalosis?

Low GFR/CrCl can decrease the kidney's ability to eliminate excess HCO3− → HCO3− accumulation → metabolic alkalosis.

How does hypokalemia contribute to metabolic alkalosis?

K+ depletion causes intracellular K+ to shift into the extracellular space; H+ shifts into cells to maintain electroneutrality → ↓ extracellular H+ → ↑ plasma pH → metabolic alkalosis.

What is the key K+/H+ shift during potassium depletion?

K+ moves OUT of cells while H+ moves INTO cells → extracellular H+ decreases → pH increases.

Which substances from the lecture can be converted to bicarbonate in the liver, and which cannot?

Acetate, citrate, and lactate can convert to HCO3−; sulfate does NOT.

How can exogenous bicarbonate contribute to metabolic alkalosis?

Administration of HCO3− increases the body's bicarbonate concentration, particularly if the kidneys cannot adequately eliminate the excess.

How do thiazide and loop diuretics contribute to metabolic alkalosis?

Both can cause dose-dependent hypokalemia → H+ shifts into cells → ↓ extracellular H+ → metabolic alkalosis.

Where do thiazide and loop diuretics act?

Thiazides act in the distal tubule; loop diuretics act in the Loop of Henle. Both can cause hypokalemia.

What is aldosterone and where is it produced?

Aldosterone is a mineralocorticoid produced in the adrenal cortex, specifically the zona glomerulosa.

What are aldosterone's major electrolyte effects?

↑ Na+ reabsorption; ↑ K+ excretion; ↑ Mg2+ excretion.

How can excess aldosterone contribute to hypertension, hypokalemia, and metabolic alkalosis?

↑ aldosterone → ↑ Na+ reabsorption → ↑ BP; ↑ K+ excretion → hypokalemia → H+ shifts intracellularly → contributes to metabolic alkalosis.

What is Apparent Mineralocorticoid Excess (AME)?

A phenomenon that produces excessive mineralocorticoid effects and can be drug-induced, leading to increased mineralocorticoid activity, hypertension, and hypokalemia.

What are two major ways bicarbonate levels can increase in the body?

Potassium depletion can promote H+ shifting into cells and increase plasma HCO3−; exogenous HCO3− or substances converted to HCO3− can directly increase the bicarbonate load.

What is the treatment approach for metabolic acidosis?

Correct the underlying cause and replace HCO3− when appropriate. Oral bicarbonate may be used for less severe states; parenteral bicarbonate may be used for more severe states.

What is the treatment approach for metabolic alkalosis?

Combat the source of HCO3− production/administration, correct contributing problems such as H+ or K+ loss, and address impaired renal elimination of excess HCO3−. Tromethamine may be used parenterally in more severe states per the lecture.

Which medications can be combined with thiazides to minimize hypokalemia?

ACE inhibitors such as lisinopril, ARBs such as valsartan, and potassium-sparing agents such as spironolactone can reduce K+ loss; amlodipine does NOT specifically minimize the hypokalemia risk.

How do lisinopril, valsartan, and spironolactone help minimize thiazide-induced hypokalemia?

Lisinopril and valsartan reduce aldosterone effects through RAAS inhibition; spironolactone directly blocks aldosterone receptors → ↓ renal K+ excretion.

What acid-base disorder should you associate with diarrhea versus vomiting?

Diarrhea → loss of HCO3− → metabolic acidosis. Vomiting → loss of H+ → metabolic alkalosis.

What acid-base disorder should you associate with DKA, lactic acid, loop/thiazide diuretics, and poor HCO3− elimination?

DKA and lactic acid accumulation → high-anion-gap metabolic acidosis. Loop/thiazide-induced hypokalemia → metabolic alkalosis. Poor renal HCO3− elimination → metabolic alkalosis.

What are the key patterns to remember for metabolic acidosis versus metabolic alkalosis?

Metabolic acidosis: ↑ H+ and/or ↓ HCO3− → ↓ pH. Metabolic alkalosis: ↓ H+ and/or ↑ HCO3− → ↑ pH.