Acid & Base

Acid-Base Regulation

Instructor Information

• Dr. Karel Alcedo

• Course: PHCY 412: Human Physiology/Pathophysiology II

• Term: Spring 2026

Background

• Cellular metabolism results in large quantities of H+ ions.
    - Catabolism of carbohydrates, proteins, and fats produces CO2.
    - CO2 readily reacts with H2O to form carbonic acid (H2CO3).
    - Carbonic acid is a weak acid that dissociates into H+ and HCO3-.

• Diet:
    - Small amounts of acid (H+) or alkali (HCO3-) can disrupt many vital body functions including:
      - Interference with hemoglobin’s ability to pick up and carry oxygen.
      - Denaturing proteins.
      - Altering neuronal activity.

Acid-Base Regulation Processes

• Three processes maintain acid-base balance:
    1. Extracellular buffers
    2. Rapid response to H+ levels through CO2 elimination from the lungs.
        - Hyperventilation vs. hypoventilation to adjust the partial pressure of CO2 (PCO2).
    3. Kidney regulation of H+/HCO3- excretion.
        - Excretion of excess H+.

Extracellular Buffers

• Plasma Buffers:
    - H2CO3/HCO3-
    - Hemoglobin

• Intracellular Buffers:
    - HPO4^2-/H2PO4-
    - Proteins
    - HCO3-/H2CO3

• HCO3- (metabolic):
    - Regulated by the kidneys through reabsorption or generation of HCO3-.
    - Normal level: 24 mEq/L

• H2CO3 (respiratory):
    - Directly proportional to PCO2.
    - Normal level: 1.2 mEq/L when arterial CO2 partial pressure (PaCO2) is 40 mmHg.
    - Buffer Ratio:
      - 20:1 ratio of HCO3-/H2CO3.
      - Blood pH = 7.4.

Proteins and Their Role in Acid-Base Balance

• Proteins:
    - Charged side chains of amino acids act as buffers.
    - More important as intracellular buffers compared to extracellular buffers.
    - Hemoglobin (Hb):
      - Binds to H+ and CO2;
      - H+ is sent to kidneys; CO2 is exhaled out via lungs.

Phosphate Buffers

• HPO4^2-/H2PO4-:
    - HPO4^2- and ammonia (NH3) are important renal buffers.
    - Bind to H+ for excretion, occurring in the distal tubule.
    - Calcium phosphate is generally inaccessible until prolonged metabolic acidosis.

Respiratory Control of Acid-Base

• Lungs eliminate CO2 through expiration.
    - Rate and depth of ventilation can be varied to adjust excretion of CO2 from diet and tissue metabolism.

• Medullary chemoreceptors in the brain stem sense changes in PCO2 and pH and modulate the control of breathing.

• Minute Ventilation:
    - Total amount of air exhaled over a 1-minute period impacts CO2 excretion and blood PCO2.

Kidney Function in Acid-Base Regulation

• Kidneys play a key role in regulating blood pH.

• Glomerulus:
    - Filters around 4,500 mEq/day of HCO3-.
    - Reabsorbed in proximal tubules to maintain acid-base balance.

• Generation of HCO3-:
    - Facilitated by carbonic anhydrase; secreted into renal capillaries.

• Excretion of H+:
    - Occurs in distal tubules.

Renal HCO3- Reabsorption & Generation

• Sodium (Na+):
    - Luminal Na+ is reabsorbed in the proximal tubule via an antiport Na+/H+ pump.
    - Na+ moves into the cell down the concentration gradient (Na+ levels are low inside the cell).
    - H+ is transported in the opposite direction.
    - H+ reacts with HCO3- in the lumen to create carbonic acid (H2CO3).
    - Carbonic Anhydrase in the lumen converts H2CO3 to CO2 and H2O.
    - CO2 then diffuses into the cells.
    - Within the cells, intracellular carbonic anhydrase converts CO2 and H2O back into H2CO3 which then dissociates into HCO3- and H+ ions.
    - HCO3- is secreted into the blood, helping to regulate pH.

Renal H+ Secretion

• H+ is secreted in the distal tubules and binds to non-volatile metabolic acids for excretion in urine.

• Examples of non-volatile acids include:
    - Lactic acid (from hypoxia or exercise).
    - Ketoacids (from diabetes).
    - Phosphoric acid (from metabolism of phospholipids & nucleic acids).
    - Sulfuric acid (from metabolism of sulfur-containing amino acids).
    - Pyroglutamic acid (from chronic acetaminophen use).

Acid-Base Disorders

• These disorders arise from abnormal changes in:
    - Ventilation:
      - Respiratory Acidosis
      - Respiratory Alkalosis
    - Plasma HCO3-:
      - Metabolic Acidosis
      - Metabolic Alkalosis

Metabolic Acidosis

• Characterized by decreased blood pH due to reduced serum HCO3-.

• Causes include:
    - Consumption of HCO3- by exogenous acids like lactic acid and ketoacids.
    - Accumulation of endogenous acids due to impaired kidney function (e.g., phosphates, sulfates).
    - Decrease in serum HCO3- due to diarrhea, biliary drainage, or pancreatic fistula.
    - Occurs secondary to rapid administration of non-alkali-containing IV fluids.

• Signs/Symptoms:
    - Headache, lethargy, coma, Kussmaul respirations, anorexia, nausea/vomiting/diarrhea (NVD), arrhythmias, hypotension.

Metabolic Alkalosis

• Characterized by increased blood pH due to elevated serum HCO3-.

• Causes include:
    - Excessive loss of metabolic acid (due to vomiting).
    - Hyperaldosteronism leading to H+ excretion from a-intercalated cells in kidneys.
    - Serum HCO3- can also rise from diuretics/excessive fluid loss or severe dehydration.
    - Overuse of antacids (sodium bicarbonate).

• Signs/Symptoms:
    - Weakness, muscle cramps, hyperactive reflexes, tetany, shallow & slow respirations, confusion, convulsions, atrial tachycardia.

Respiratory Acidosis

• Characterized by decreased blood pH due to elevated serum CO2.

• Defined by a PaCO2 greater than 45 mmHg.

• Causes include:
    - Hypoventilation due to drugs, head injuries, respiratory muscle paralysis, chest wall disorders (e.g., kyphoscoliosis, broken ribs), and lung disorders (e.g., pneumonia, pulmonary edema, emphysema, asthma, bronchitis).

• Signs/Symptoms:
    - Headache, blurred vision, breathlessness, restlessness, apprehension, lethargy, disorientation, muscle twitching, tremors, convulsions, coma.

Respiratory Alkalosis

• Characterized by increased blood pH due to decreased serum CO2.

• Defined by a PaCO2 less than 35 mmHg.

• Causes include:
    - Hyperventilation due to pulmonary disease, congestive heart failure, high altitudes, fever, anemia, thyrotoxicosis, early salicylate intoxication, hysteria, cirrhosis, and sepsis.

• Signs/Symptoms:
    - Nervous system stimulation causing dizziness, confusion, paresthesia, convulsions, and coma.
    - Symptoms of spasms, tetany, and hypocalcemia.

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