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Maintenance of pH of the Body - Short Notes

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What is pH and Why Does It Matter?

• pH is a measure of how acidic or basic a fluid is.
• Normal blood (arterial) pH = 7.35 to 7.45 (slightly alkaline)
• Intracellular pH = 7.0 to 7.3
• Even small changes outside this range can disrupt enzymes, proteins, and cell function - this is why the body controls pH so tightly.

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How Much Acid Does the Body Produce Daily?

• Animal food = net acid load
• Plant food = net alkaline load
• Net non-volatile acid production = ~1 mmol H+ per kg body weight per day

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3 Main Ways the Body Maintains pH

1. Buffer Systems (First Line of Defense - Fastest)

• When acid (HA) is added:

  HA + NaHCO3 → NaA + H2O + CO2

• The CO2 is blown off by the lungs, keeping pH stable.
• HCO3- acts as the "sponge" that absorbs the acid.

• Plasma proteins - in the blood
• Phosphate ions - in blood and urine
• Hemoglobin - inside red blood cells
• Bone - in chronic metabolic acidosis, bone dissolves to release alkali (but causes osteoporosis long-term)
• Intracellular buffers - hemoglobin, cell proteins, organophosphates

Buffers only minimize pH change - they do NOT remove acid from the body.

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2. Respiratory System (Second Line - Acts Within Minutes)

pH depends on the ratio of HCO3- to CO2

• Acidosis (low pH) → brain detects it → breathing speeds up → more CO2 blown out → pH rises back up
• Alkalosis (high pH) → breathing slows down → CO2 retained → pH falls back down

• In metabolic acidosis: for every 1 mmol/L fall in HCO3-, PaCO2 drops by 1.2 mmHg
• In metabolic alkalosis: for every 1 mmol/L rise in HCO3-, PaCO2 rises by 0.7 mmHg

Respiratory compensation is fast but usually does not fully normalize pH on its own.

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3. Kidneys (Third Line - Slowest but Most Powerful)

NAE = NH4+ excreted + Titratable acids excreted - HCO3- excreted

• Normally the kidney reabsorbs all filtered HCO3- (mainly in the proximal tubule)
• If blood is too acidic → kidneys make and secrete more H+ → regenerate new HCO3- → blood pH rises
• If blood is too alkaline → kidneys excrete HCO3- in urine

Kidney compensation takes hours to days but provides the most thorough correction.

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Summary Table

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Easy Memory Trick

"BBR" - Buffers soak, Breathing blows, Renal removes

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Key Values to Remember

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Renal Physiology: Maintenance of pH - Short Notes (Easy Words)

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Why the Kidney is Special

• Buffers and lungs only minimize or temporarily fix pH changes
• The kidney is the only organ that permanently removes acid from the body
• It is the slowest but most powerful controller of pH
• Normal blood pH = 7.35 to 7.45
• Daily acid load from diet and metabolism = ~1 mEq/kg/day (about 35-70 mEq total per day)

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What the Kidney Must Do

1. Reabsorb (recover) almost all the bicarbonate (HCO3-) filtered at the glomerulus - so it is not lost in urine
2. Regenerate new HCO3- to replace what is used up neutralizing daily acid production

Think of it this way: your blood uses HCO3- as a sponge to soak up acid every day. The kidney makes a fresh sponge each day and sends it back to the blood.

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Net Acid Excretion (NAE) Formula

NAE = NH4+ + Titratable Acid - HCO3-

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Part 1 - Bicarbonate Reabsorption Along the Nephron

How Proximal Tubule Reabsorbs HCO3- (Simple Steps)

1. Tubule cell pumps H+ into the lumen via the NHE3 exchanger (H+ out, Na+ in)
2. In the lumen: H+ + HCO3- → H2CO3 (carbonic acid)
3. Carbonic anhydrase IV (on brush border) breaks it down: H2CO3 → CO2 + H2O
4. CO2 freely enters the cell
5. Inside the cell: Carbonic anhydrase II reforms: CO2 + H2O → HCO3- + H+
6. HCO3- exits to blood via NBC1 cotransporter (with Na+)
7. The H+ goes back to step 1

Key point: Carbonic anhydrase (CA) is essential here. Block CA with acetazolamide → HCO3- is lost in urine → urine becomes alkaline.

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Part 2 - Titratable Acid Excretion (~40% of NAE)

• Some weak acid buffers are filtered at the glomerulus (mainly phosphate - HPO4²-)
• As H+ is secreted into tubular fluid, it combines with these buffers:

  H+ + HPO4²- → H2PO4- (excreted in urine)

• This H+ is now "trapped" in urine and cannot come back
• Called "titratable" because you can measure it by titrating urine back to blood pH with alkali

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Part 3 - Ammonium (NH4+) Excretion (~60% of NAE)

Simple Steps:

1. Proximal tubule cells take up glutamine (amino acid from blood)
2. Glutamine is broken down → makes 2 NH4+ + 2 HCO3- per molecule
3. NH4+ is secreted into the tubular lumen (via NHE3, replacing H+)
4. The new HCO3- goes back to the blood (this is the "new" bicarbonate)
5. In the thick ascending limb, NH4+ is reabsorbed into the medullary interstitium
6. NH3 (gas form) diffuses back into the collecting duct lumen
7. In the collecting duct, H+ secreted by alpha-IC cells meets NH3:

   NH3 + H+ → NH4+ (trapped in urine and excreted)

Key insight: For every NH4+ excreted, the kidney generates one "new" HCO3- to replenish the blood buffer. This is the kidney actually making new alkalinity.

• Acidosis
• Hypokalemia

• Hyperkalemia
• Chronic kidney disease (major reason CKD causes metabolic acidosis)

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Part 4 - The Collecting Duct: Fine-Tuning of pH

How α-IC Cell Works (in Acidosis):

1. Inside cell: CO2 + H2O → H+ + HCO3- (via carbonic anhydrase II)
2. H+ pumped into tubular lumen via H+-ATPase (ATP-powered proton pump)
3. H+ titrates NH3 and phosphate in urine → trapped as NH4+ and H2PO4-
4. HCO3- exits basolateral side to blood via AE1 exchanger (Cl-/HCO3-)
5. Net result: acid removed from body, blood gets new HCO3-

Hormonal Control:

• Aldosterone stimulates Na+ absorption by principal cells → makes lumen more electrically negative → drives more H+ secretion by α-IC cells
• Chronic metabolic acidosis converts β-IC cells into α-IC cells → more acid-secreting cells

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Summary: Kidney's 3 Tools to Control pH

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Key Numbers to Remember

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Easy Memory: "The 3 R's of Renal pH Control"

Reabsorb HCO3- (don't lose the buffer) Remove acid via phosphate (titratable acids) Regenerate new HCO3- via ammonium excretion

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