Regulation of Acid-Base Balance

Overview

The regulation of acid-base balance is essential for maintaining physiological homeostasis. The body must tightly control plasma pH to ensure proper function of enzymes, nerve cells, and metabolic processes. Acid-base disturbances can lead to serious clinical consequences, including acidosis and alkalemia.

Plasma pH

Definition and Normal Range

• Plasma pH is a measure of hydrogen ion concentration in the blood.

• The formula for pH is:

• Normal plasma pH: 7.38–7.42

• Alkalemia: pH > 7.45 (low [H+])

• Acidemia: pH < 7.35 (high [H+])

Effects of Abnormal pH

• Enzyme activity

• Nerve function

• Membrane transport

• Metabolic functions

• Most biological functions

Clinical Implications

• Acidosis can be metabolic or respiratory in origin.

• Alkalosis can also be metabolic or respiratory.

How Acids and Bases Are Added to the Body

Sources of Acid Input

• Diet: Fatty acids, amino acids

• Metabolism: CO2 (from cellular respiration), lactic acid, ketoacids

Buffer Systems

• Bicarbonate (HCO3-) in extracellular fluid

• Proteins, hemoglobin, phosphates in cells

• Phosphates, ammonia in urine

Buffer Capacity

• Buffer capacity is the efficiency of a buffer in resisting changes in pH.

Types of Acid Loads: Volatile vs Non-Volatile Acids

Volatile Acids

• Excreted by the respiratory system.

• Main example: Carbonic acid (H2CO3) formed from CO2 and H2O.

• Equation:

• Approximately 20 moles/day excreted via lungs.

Non-Volatile Acids

• Excreted by the renal system.

• Produced by metabolism of certain amino acids (e.g., cysteine, methionine, histidine).

• Cannot be excreted by ventilation.

• Examples: Sulfuric acid (H2SO4), Hydrochloric acid (HCl)

Normal Acid Load

Daily Acid Production

• Volatile acid load: ~20 moles/day (from CO2 production)

• Non-volatile acid load: much less, but significant for renal excretion

Metabolic Pathways

• Carbohydrate metabolism produces CO2 (volatile acid)

• Metabolism of amino acids like cysteine and methionine produces non-volatile acids

• Amino acids like alanine do not contribute to acid load

Time Dependence of Whole Body Response to an Acid Load

Immediate and Delayed Responses

• Initial buffering by extracellular and intracellular buffers

• Movement of H+ into cells

• Renal excretion of H+ to restore balance

Compensatory Mechanisms

• Respiratory compensation: changes in ventilation to alter CO2 excretion

• Renal compensation: increased H+ secretion and HCO3- reabsorption

Renal Conservation of Bicarbonate

Mechanisms in the Proximal Tubule

• Bicarbonate reabsorption: prevents loss of buffer in urine

• Sodium-coupled solute reabsorption: includes glucose, phosphate, and other nutrients

• Sodium-proton counter transport: exchanges Na+ for H+

• Sodium-glucose cotransport: reabsorbs glucose with sodium

Urinary Buffer Systems

• Phosphate Buffer System:

• Ammonia Buffer System:

• Buffers allow excretion of acid without excessive loss of water

Efficiency of Acid Excretion

• Excreting free H+ is inefficient and would require large urine volumes

• Buffering allows efficient acid excretion

Summary Table: Volatile vs Non-Volatile Acids

Cellular Sensing of Acid-Base Status

Mechanisms

• Renal tubular cells sense changes in pH and bicarbonate

• Intracellular pH shifts trigger changes in transporter expression and activity

• Increased H+ secretion and bicarbonate reabsorption during acidosis

• Ammonium production increases during acidosis

Regulation of Water, Sodium, and Acid-Base Balance

Key Sensors and Effectors

• Osmoreceptors in hypothalamus sense plasma osmolality

• Baroreceptors in afferent arteriole and carotid sense circulating volume

• Chemoreceptors in brainstem and carotid bodies sense pH and CO2 levels

• Renal tubular cells sense changes in acid-base status

Key Equations

• pH calculation:

• CO2 hydration:

• Phosphate buffering:

• Ammonia buffering:

Additional info: Academic context and expanded explanations have been added to clarify mechanisms and clinical relevance.