acid base balance

pH and acid base balance

• pH = measured as -log10[H+] or log 1/[H+]

• Neutral pH is 7.0

• Acid is below 7, Alkaline above 7

• Acid donates protons, alkali (base) can accept

• Stronger the acid → greater % molecules separate to free H+ and anions

• Cell pH of about 7 is necessary for normal cell function

Enzyme functions in body are highly sensitive to hydrogen ion concentration ([H+]). Slight deviations change:

• protein structure

• enzyme activity

• nerve excitability

determinants of pH

Blood pH depends only on the ratio of [HCO3-] to [H₂CO₃]

H₂CO₃ = carbonic acid

– Weak acid, a portion dissociates into H+ and HCO3-

– Can form from either CO₂ + H₂O or from H+ + HCO3-

HCO3^- = bicarbonate ion

– H₂CO₃ part-dissociates into HCO₃- and H+

– CO₂ combines with OH- (forming HCO₃-, by carbonic anhydrase)

– carbonate (CO₃^2- combines with H⁺)

CO2 + H2O H2CO3 H+ + HCO3-

changes in pH

Alterations in body pH can occur due to:

• Metabolism in all tissue – continuous production of CO2

• Breakdown of food – protein, other organic minerals etc (phosphorus and sulphur – phosphorus and sulphuric acid)

• Metabolic intermediaries – lactic acid in exercise

How does the body deal with such changes? Existence of a buffering system

• Bicarbonate buffer system – MAJOR SYSTEM!

• The phosphate buffer system

• Heamoglobin buffer system

• Plasma and cell protein buffer system

regulation of blood pH

• Tightly regulated process primarily involving the kidney and the lungs

• Lungs – releasing CO2

• Kidneys – regulation of HCO3-

• Pathology of the respiratory and renal system will lead to acid base imbalance

role of renal system in pH balance

Regulation of pH by the renal system is done by:

• Reabsorbing filtered bicarbonate (HCO₃-)

• Synthesis of new bicarbonate (HCO₃-)

• Tubular secretion of H+

bicarbonate reabsorption in the nephron

first pic

• Tubular cells normally reabsorb all the filtered HCO3-

• Mostly at the proximal tubule (about 80%)

• Remainder in the loop of Henle and distal loop (about 20%)

second pic

• Once reabsorbed HCO3- is in the interstitial space

• Need to be reabsorbed back into the peritubular capillaries

Occurs via

• Na+/ HCO3- co transporters (proximal tubule)

• Cl-/ HCO3- exchanger (collecting tubules)

bicarbonate synthesis

This diagram shows how the kidneys generate "new" bicarbonate (HCO₃⁻) to balance body pH while excreting acid (H⁺) using a phosphate buffer.

1. Inside the Tubular Cell (Synthesis)

• Water splits: H₂O inside the cell dissociates into H⁺ and OH⁻.

• Carbon dioxide sources: CO₂ enters from cellular metabolism or blood plasma.

• Bicarbonate formation: Carbonic anhydrase (ca) combines CO₂ and OH⁻ to form HCO₃⁻.

• Blood absorption: This "new" HCO₃⁻ moves directly into the peritubular capillary blood to buffer systemic acidity.

2. In the Tubular Lumen (Acid Elimination)

• Active transport: An ATP-driven pump actively pushes the remaining H⁺ ion out of the cell and into the urine filtrate.

• Phosphate buffering: The secreted H⁺ binds with filtered monohydrogen phosphate (HPO₄²⁻).

• Excretion: This forms dihydrogen phosphate (H₂PO₄⁻), safely trapping the acid to be excreted in urine.

H+ secretion

• Most excreted H+ gains entry to tubular system from being actively secreted

• H+ is secreted into the tubular filtrate by the proximal, distal and collecting tubules

• H+ secretion increases when pH is low (or CO₂ is high) and decreases when pH is high.

• No mechanism of reabsorption of H+

secretion of H+

Electrogenic H+ pump

• ATP-driven H+ pump (CD)

Na-H+ exchanger

• Proximal tubule, DT, CD

• H+ secreted in exchange for Na+

H+ - K+ exchanger

• Electroneutral pump exchanging H+ for K

excretion of bicarbonate

This diagram shows how Type B intercalated cells secrete excess bicarbonate (HCO₃⁻) into urine during alkalosis while reabsorbing acid (H⁺) back into the blood.

1. Inside the Intercalated Cell (Synthesis)

• Water splits: H₂O inside the cell dissociates into H⁺ and OH⁻.

• Carbon dioxide sources: CO₂ enters from cellular metabolism or blood plasma.

• Bicarbonate formation: Carbonic anhydrase (ca) combines CO₂ and OH⁻ to form HCO₃⁻.

2. In the Tubular Lumen (Base Elimination)

• Anion exchange: A transporter exchanges intracellular HCO₃⁻ for luminal Cl⁻.

• Bicarbonate excretion: The HCO₃⁻ enters the urine filtrate for elimination.

3. In the Peritubular Plasma (Acid Reabsorption)

• Active proton pumping: ATP-driven pumps push H⁺ out into the blood.

• Potassium reabsorption: One pump exchanges H⁺ for incoming K⁺ ions.

• Chloride shift: Cl⁻ leaves the cell through channels into the blood.

acidosis and alkalosis

Acidosis is an abnormal process that produces acidaemia – Low pH

• Respiratory acidosis – this is a low pH where primary defect is an increase in the pCO2

• Metabolic acidosis – this is a low pH where the primary defect is a decrease in plasma HCO3-

Alkalosis is an abnormal process that produces alkalaemia – High pH

• Respiratory alkalosis – this is high pH where primary defect is a decrease in pCO2

• Metabolic alkalosis – this is high pH where primary defect is an increase in plasma HCO3

acidosis

Compensatory response in respiratory acidosis

• pCO2 has increased and therefore blood pH has fallen

• Kidneys will attempt to bring about an increase in plasma HCO3^-

• Known as renal compensation

Compensatory response in metabolic acidosis

• Plasma HCO3- has decreased and therefore blood pH has fallen

• Lungs will increase ventilation, rate of breathing leading to a decrease in pCO2

• Known as respiratory compensatio

alkalosis

Compensatory response in respiratory alkalosis

• pCO2 has decreased and therefore blood pH has risen

• Kidneys will decrease in H+ secretion

• Only some HCO3- is reabsorbed but rest excreted. Tubular synthesis of HCO3- is decreased.

• This is renal compensation

Compensatory response in metabolic alkalosis

• HCO3- has increased and therefore blood pH has increased

• Lungs will increase level of pCO2 by reducing rate of breathing and ventilation.

• This is respiratory compensation