13 - Acid-Base Regulation

normal values

• pH = 7.35-7.45

• pCO₂ = 40mmHg

• HCO₃^- = 24 mEq/L

• anion gap = 8-16 mEq/L

• CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃^-

pH

pH = [HCO₃^-] / pCO₂

• more basic/alkaline → high HCO₃^-, low pCO₂

• more acidic → low HCO₃^-, high pCO₂

volatile acid

CO₂ is a volatile acid, generated by oxidation of carbohydrates, fats, and amino acids

• doesn’t contain H⁺ but is considered an acid because it makes H₂CO₃

non-volatile acids / fixed acids

all other acids other than CO₂

• inorganic acids → produced during nutrient/protein metabolism

  • sulfuric acid (H₂SO₄) and phosphoric acid (H₃PO₄)

• organic acids → result from intermediary metabolism

  • lactic acid (exercise), fatty acids (carboxylic acid), fat burn down (keto acids)

defense against changes in pH

• plasma buffering system → initially neutralizes H⁺

• lungs → rapid removal of volatile acids

• kidneys → long-term regulation of acid-base

plasma buffering system

initially neutralizes H⁺

• HCO₃^- system → major buffer of the body, first-line defense against H⁺

• hemoglobin buffering system → RBCs take up CO₂, H⁺ binds hemoglobin

  • plays big role in CO₂ transport and removal

• protein buffering system → major buffer in intracellular fluid

• phosphate buffering system → HPO₄^2- and H₂PO₄^- important in kidney tubules

lung regulation of pH

CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃^-

• rapid removal of volatile acids by removing CO₂ and eliminating H₂CO₃

• chemoreceptors detect changes in H⁺, O₂, and CO₂ levels to regulate respiration

• acidotic pH → respond with increased respiration

  • blows off more CO₂

  • reduces volatile acids and H⁺

• alkalotic pH → respond with decreased respiration

  • blow off less CO₂

  • increases volatile acids and H⁺

kidney regulation of pH

long-term regulation of acid-base by adjusting H⁺ and HCO₃^-

• filter and excrete nonvolatile (fixed) acids

• secrete and excrete H⁺

• reabsorb filtered HCO₃^-

• generate new HCO₃^- → coupled to NH₄⁺ synthesis and titratable acids

HCO₃^- reabsorption in proximal tubule

reabsorption of HCO₃^- in proximal tubule is dependent on H⁺ secretion, with 80% reabsorbed in proximal tubule (recycling of HCO₃^-)

• in the lumen (apical)

  • H⁺ is pulled out of cell via Na⁺/H⁺ exchanger and H⁺-ATPase

  • H⁺ combines with HCO₃^- to form H₂CO₃

  • H₂CO₃ converts to water and CO₂ via carbonic anhydrase 4 and 14

  • water and CO₂ passively diffuse into cell

• in proximal tubule cell

  • water and CO₂ combine via carbonic anhydrase 2 to form H₂CO₃

  • H₂CO₃ breaks down into H⁺ and HCO₃^-

• in the blood (basolateral)

  • HCO₃^- is transported into cell via Na⁺ co-transporter or Cl^- counter-transporter

HCO₃^- production in collecting duct

⍺-intercalated cells secrete H⁺ into the lumen and reabsorb HCO₃^- in the blood

• water and CO₂ combine via carbonic anhydrase in the cell to make H₂CO₃

• H₂CO₃ dissociates to form H⁺ and HCO₃^-

  • HCO₃^- is newly formed enters the bloodstream

  • H⁺ is secreted via H⁺-ATPase or H⁺/K⁺ pump to react with NH₃ and titratable acids

titratable acids

titratable acids are conjugate bases of phosphoric acid, sulfuric acid, urate, citrate, uric acid, and other filtered fixed acids

• reacts with H⁺ in nephron lumen and excreted

• mainly filtered but are also secreted and reabsorbed

  • remain in nephron lumen during acidosis to react with and excrete more H⁺

NH₃ synthesis in proximal tubule

during acidosis, NH₃/NH₄⁺ generation increases to buffer acid

• in the cell:

  • glutamine from liver enters via Na⁺/glutamine co-transporter 

  • glutaminase in mitochondria breaks into 2 NH₄⁺ and α-ketoglutarate

    • ⍺-ketoglutarate is converted into 2 HCO₃^- during gluconeogenesis

• in the lumen (apical):

  • NH₄⁺ is secreted via Na⁺/NH₄⁺ transporter

  • NH₄⁺ can dissociate into H⁺ and NH₃ gas that diffuses across membrane

    • NH₃ reacts with H⁺ in the nephron lumen, especially in the collecting duct

• in the blood (basolateral):

  • HCO₃^- is transported into bloodstream via Na⁺/HCO₃^- co-transporter

anion gap

important diagnostic tool for metabolic acidosis, the imbalance of HCO₃^-

• anion gap = [Na⁺] - ( [Cl^-] + [HCO₃^-] ) 

• normal range: 8-16 mEq/L

• anion gap is not equal to 0 due to unmeasured anions

  • increasing fixed acids (anions) will lower bicarbonate → increased anion gap

metabolic acidosis and anion gap

• high anion gap → increased fixed acids drives down HCO₃^- levels

  • caused by lactic acid, diabetes mellitus, poisoning, chronic renal failure

• normal anion gap → decreased HCO₃^- levels leave fixed acids unbuffered

  • kidneys and GI compensate for HCO₃^- loss by increasing Cl^- reabsorption

  • caused by GI loss of HCO₃^- and renal tubular dysfunction

• low anion gap → decreased plasma proteins

  • albumin is negatively charged, where its loss causes retention of negatively charged ions

  • caused by hemorrhage, liver cirrhosis, nephrotic syndrome