Lecture 3 - pH Balance

Compounds near-zero in urine

Protein and glucose

Compounds rich in urine

Potential toxins and metabolic wastes (K, H, urea, ammonia)

pH of blood

7.35 - 7.45; tight range

Basic pH

Alkalosis (above 7.45)

Symptoms of alkalosis

Confusion, vomiting, muscle spasms

Acidic pH

Acidosis (below 7.35)

Symptoms of acidosis

Weakness, nausea, vision loss, coma

Sub-clinical acidosis

Increases susceptibility to osteoporosis and CKD

Acid deteriorates bone and kidneys are overwhelmed

Daily Acid Load Factors

1. Metabolism

2. Diet

3. Base loss (excretion)

4. Disease (additional base loss)

Daily acid load is…

Higher than permissible deviation requiring regulation

Buffers

Chemical reaction that protects blood pH from daily acid load by neutralizing excess acids or bases

Buffering power =

Change in H⁺/change in pH

Less change in pH means…

Stronger buffer

Major blood buffer system

CO₂/HCO₃^- (sodium bicarbonate)

Other buffer systems

Proteins and phosphate

Henderson-Hasselbach

pH = pK + log[HCO_3^-]/[CO₂]

(log [A/B])

What organ produces bicarbonate?

Kidneys

Bicarbonate reacts with…

Excess protons, forming CO₂ that is exhaled by lungs

What happens to CO₂?

It is exhaled by the lungs, which is why respiratory rate influences blood pH

What type of buffering system is the body?

OPEN - CO₂ does not build up with adequate ventilation, which drives the reaction forward

Without bicarbonate…

The blood pH would decrease drastically

If CO₂ cannot escape (COPD)…

pH would be pathologically lower than it should be because CO₂ is acidic

Kidneys main roles:

1. Generate bicarb (HCO₃^-)

2. Reabsorb bicarb (not lost in urine)

3. Excrete protons

Proximal tubule function

Reabsorbs most of the filtered bicarbonate and generates new bicarbonate

Collecting duct function

Generate extra bicarb and excrete extra protons if needed

What does the body respond to?

DIRECTLY to pH, CO₂, and HCO₃^- changes (not hormones)

What structure creates new HCO₃^-?

The proximal tubule epithelia (and somewhat collecting duct)

Enzyme involved in bicarb production:

Carbonic anhydrase

What molecule do protons react with to get into urine?

Phosphate

Creating bicarb with CO₂ produces…

PROTONS (H⁺)

Creating bicarb with glutamine produces…

Ammonium (NH₄⁺)

Bicarb reabsorption

After interaction with H → CO₂ which is membrane permeable → reacts with carbonic anhydrase to form HCO₃ in kidney → Blood via sodium symport

Collecgting duct function during acidosis:

Secretion of protons and generate more bicarbonate

Transporter in proximal tubule

Na/HCO₃ symport

What cells produce bicarb in collecting duct?

alpha-intercalated (“acid-secreting” cells)

Transporter in collecting duct

Cl/Bicard antiport

After neutralization…

The kidneys need to secrete protons (don’t want buildup of molecular hydrogen)

pCO₂

Partial pressure of carbon dioxide sensed by chemoreceptors to maintain blood pH in ALVEOLI

High CO₂ affect on ventilation

Increases rate so that more CO₂ is exhaled and prevent acidic pH

Low CO₂ affect on ventilation

Slows ventilation to retain CO₂ and prevent basic pH

Venous vs. arterial CO₂ concentration

High vs. low

Chemoreceptors

• Monitors changes in pH, alveolar CO₂, and HCO₃

• Located in the brainstem

Chemoreceptors fire when…

CO₂ levels are high

What two molecules are essential to regulate pH?

Carbon dioxide and bicarbonate

Types of pH Imbalance

• Metabolic (acidosis and alkalosis from H or bicarb)

  • Diabetes

• Respiratory (CO₂)

  • COPD

Metabolic acidosis cause

Low bicarbonate: diabetes, diarrhea, CKD (impaired production or loss)

Respiratory acidosis cause

Too much CO₂: poor/slow ventilation from COPD/sleep apnea

Metabolic alkalosis cause

Bicarb overproduction: vomiting

Respiratory alkalosis cause

Not enough CO₂: hyperventilation

Metabolic acidosis compensation

Hyperventilation (decrease CO₂)

Respiratory acidosis compensation

More bicarb production in kidneys

Metabolic alkalosis compensation

Hypoventilation (increase CO₂)

Respiratory alkalosis compensation

Decrease bicarb reabsorption in kidneys

Respiratory vs. Renal Compensation

Quicker due to chemoreceptor response vs. slower

Treatments for acidosis

1. Bicarbonate supplement (ex. Tums) for acute cases

2. Diet changes (less acidic foods in diet)

3. Artificial ventilation if respiratory cause

Altitude Sickness

• Low air pressure causes hyperventilation and decrease in CO₂

  • Acid-base imbalance, need to decrease bicarb

• Treated with acetazolamide (inhibits carbonic anhydrase)

Acetazolamide

• Inhibits carbonic anhydrase to reduce reabsorption and production of bicarb

• Treatment for altitude sickness