Acid-Base Physiology: pH Balance

Acid-Base Physiology Overview

• Focuses on the body's management of acids and bases to maintain pH balance

Learning Objectives

• Identify major acid sources in the body
• Name the body's three major chemical buffer systems and their pH change resistance
• Describes the respiratory system's impact on acid-base balance
• Explains how kidneys regulate hydrogen and bicarbonate ion concentrations in the blood
• Differentiates between acidosis and alkalosis from respiratory and metabolic factors
• Describes the mechanisms of respiratory and renal compensations for acid-base disturbances

Acid vs. Base

• Acid: A chemical substance that can donate H+ ions, examples including CH3COOH and NH4+
• Base: A chemical substance that can accept H+ ions, examples including CH3COO- and NH3
• The term alkali is interchangeable with base
• pH is inversely related to H+ concentration
• Average plasma H+ level is 0.00004 mEq/L
• pH = log(1/[H+]) = -log[H+]
• At a concentration of 0.00000004, the pH equals 7.4

Hydrogen Ion Concentration

• Must be precisely regulated
• Arterial blood pH is about 7.4
• Venous and interstitial fluid pH is about 7.35
• Intracellular fluid pH ranges from 6.0 to 7.4
• Urine pH ranges from 4.5 to 8.0
• H+ concentration in body fluids is kept low
• Protons significantly affect biochemical reactions and physiological processes critical for homeostasis

Effects of pH Changes

• Small pH changes can have substantial physiological consequences
• Molecules contain chemical groups that can donate H+ and act as weak acids (R-COOH -> R-COO- + H+) or accept H+ and act as weak bases (R-NH2 + H+ -> R-NH3)
• pH shifts can alter biological activity by changing net electrical charge, either directly or indirectly (altering molecular conformation)

pH-Sensitive Molecules

• Variety includes enzymes, receptors and their ligands, ion channels, transporters, and structural proteins
• Na-K pump activity decreases by half with a ~1 pH unit shift from the resting pH
• Phosphofructokinase activity decreases by ~90% with a pH drop of only 0.1
• Cell proliferation may decrease as much as 85% with a 0.4 drop

Acid-Base Balance

• Metabolic processes provide hydrogen ions
• Aerobic and anaerobic respiration of glucose produces carbonic and lactic acid, respectively
• Incomplete oxidation of fatty acids produces acidic ketone bodies
• Oxidation of sulfur-containing amino acids produces sulfuric acid
• Hydrolysis of phosphoproteins and nucleic acids produces phosphoric acid
• Metabolism has few sources of bases
• Fruits and vegetables contain anions that metabolize to HCO3-

Alkalosis vs Acidosis

• Alkalosis: Excess removal of H+ from body fluids
• Acidosis: Excess addition of H+ in body fluids

Body's Defense Against pH Changes

• Chemical buffers are the first line of defense
• Ventilation is the second line of defense
• Renal regulation is the third line of defense
• Ventilation accounts for 75 % of pH disturbances as a rapid, reflexively controlled response
• Kidneys don't correct pH disturbances as quickly as the lungs

Chemical Buffers

• Includes proteins, phosphate ions, and HCO3-
• Intracellular and extracellular protein buffers: Plasma proteins, hemoglobin
• Phosphate buffer: in renal tubular fluids, intracellular fluids
• Bicarbonate buffer: CO2 + H2O <-> H2CO3 <-> H+ + HCO3-
• Reaction occurs in all cells and plasma
• In lungs, renal tubules, and RBCs, high carbonic anhydrase concentration speeds up the reaction
• A buffer moderates, but a buffer does not prevent changes in pH by combining with or releasing H+

Protein Buffers

• Hemoglobin and albumin are the most abundant buffer in intracellular fluid and blood plasma
• Free carboxyl groups (COO-) can act as proton acceptors
• Free amino groups (NH3+) can donate protons
• Proteins are amphoteric, allowing them to function as both acids and bases

Hemoglobin Buffer System

• Hb binds and transports H+ and CO2
• Carbonic anhydrase is part of this system
• Chloride shift involves chloride-bicarbonate exchange

Respiratory and Renal Compensation

• The body responds to acid-base imbalances through compensation
• Hyperventilation or hypoventilation aid metabolic problems in respiratory compensation
• Renal mechanisms can bring about metabolic compensation for respiratory problems

Respiratory Compensation for Metabolic Acidosis

• Increased ventilation is a respiratory compensation for acidosis
• Ventilation is directly affected by plasma H+ levels and pCO2 through carotid and aortic chemoreceptors
• Increased H+ stimulates chemoreceptors, signaling medullary respiratory control centers to increase ventilation
• Increased alveolar ventilation allows the lungs to excrete more CO2 and convert H+ to carbonic acid

Central Chemoreceptors

• Medulla oblongata chemoreceptors cannot directly respond to plasma pH changes because H+ does not cross the blood-brain barrier
• Changes in plasma pH change PCO2
• CO2 stimulates the central chemoreceptors

Renal Regulation of pH Balance

• Involves secretion of H+
• Involves production of new HCO3-
• Involves reabsorption of HCO3-
• Ammonia from amino acids and phosphate ions (HPO42-) act as buffers in the tubule, trapping H+ as ammonium (NH4+) and H2PO4-
• These buffers allow greater H+ excretion
• Urine can become acidic, pH of about 4.5.

Acid-Base balance and Transport

• HCO3- and H+ transporters are located on different faces of the epithelial cell
• During periods of acidosis, type A intercalated cells secrete H+ and reabsorb bicarbonate
• During periods of alkalosis, type B Intercalated cells secrete HCO3- and reabsorb H+

Acid-Base Disturbances: Potassium

• Disturbances can affect blood K+ concentration by altering K+ secretion by the principal cells
• Alkalosis increases K+ secretion
• Acidosis decreases K+ secretion