[26.4 - 26.4] Fluid, electrolyte, acid base balance (2026)
Acid-Base Balance Overview
Importance of pH Regulation
pH affects all functional proteins and biochemical reactions in the body.
The body closely regulates pH to maintain optimal conditions for cellular functions.
Normal pH Values
Arterial Blood: pH = 7.4
Venous Blood and Interstitial Fluid: pH = 7.35
Intracellular Fluid (ICF): pH = 7.0
Definitions of Acid-Base Conditions
Alkalosis (Alkalemia): arterial pH > 7.45
Acidosis (Acidemia): arterial pH < 7.35
Note: pH 7.35 is not considered acidic as per the pH scale, but it indicates a higher H+ concentration than optimal, thus termed physiological acidosis.
Sources of Hydrogen Ion (H+) Production
Dietary Intake: Small amounts of acidic substances enter the body through food.
Metabolic by-products: Most H+ is produced as a by-product of metabolism.
Phosphorus-containing protein breakdown releases phosphoric acid into the extracellular fluid (ECF).
Lactic acid is produced during anaerobic respiration of glucose.
Fatty acids and ketone bodies come from fat metabolism.
H+ is released when CO₂ is converted to bicarbonate (HCO₃–) in blood.
Regulation of Hydrogen Ion Concentration
Mechanisms of Regulation: The concentration of hydrogen ions is regulated by three sequential mechanisms:
Chemical Buffer Systems: First line of defense, acts rapidly.
Brain Stem Respiratory Centers: Act within 1-3 minutes.
Renal Mechanisms: Most potent but require hours to days to effect pH changes.
Chemical Buffer Systems
Acids: Proton donors.
Strong acids dissociate completely in water, liberating all their H+ and dramatically affecting pH.
Weak acids dissociate partially and efficiently prevent pH changes, functioning as chemical buffers.
Strong Bases: Easily dissociate in water and quickly tie up H+.
Weak Bases: Accept H+ more slowly than strong acids.
Role of Chemical Buffers
Definition: A chemical buffer is a system comprising one or more compounds that resist pH changes when strong acids or bases are added.
Buffers bind H+ if pH drops and release H+ if pH rises.
Types of Major Buffering Systems:
Bicarbonate Buffer System: Involves H₂CO₃ (carbonic acid, a weak acid) and NaHCO₃ (sodium bicarbonate, a weak base).
Phosphate Buffer System: Involves sodium salts of dihydrogen phosphate (H₂PO₄–, a weak acid) and monohydrogen phosphate (HPO₄²–, a weak base).
Protein Buffer System: Intracellular proteins, which are amphoteric (able to function as both acids and bases).
Bicarbonate Buffer System
Function:
Buffers both ICF and ECF but is primarily important as an ECF buffer.
Mechanism:
If a strong acid is added, HCO₃– binds to H+ forming H₂CO₃, causing only a slight decrease in pH.
HCO₃– levels are regulated by the kidneys.
If a strong base is added, H₂CO₃ dissociates to donate H+, causing only a slight increase in pH and ties up the base (example: OH–).
H₂CO₃ is almost limitless due to CO₂ released by respiration.
Phosphate Buffer System
Function and Action:
Action is similar to the bicarbonate buffer system but is primarily effective in urine and intracellular fluid (ICF) due to high phosphate concentrations.
H+ released by strong acids is tied up by weak acids.
Strong bases are converted to weak bases.
Protein Buffer System
Overview:
Intracellular proteins are the most plentiful and powerful buffers, with plasma proteins also contributing.
Protein molecules are amphoteric and can act as both weak acids and weak bases.
Mechanism:
When pH rises, carboxyl (COOH) groups can release H+.
When pH falls, amino (NH₂) groups can bind H+.
Hemoglobin functions as an intracellular buffer.
Respiratory Regulation of H+
Both respiratory and renal systems serve as physiological buffers, but act slower than chemical buffers yet provide more powerful buffering effects.
The respiratory system eliminates CO₂ (considered an acid):
A reversible equilibrium exists in blood (CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃– + H+).
During CO₂ unloading, the reaction shifts to the left, and H+ is incorporated into H₂O.
During CO₂ loading, the reaction shifts to the right, and H+ is buffered by proteins.
Regulation in Response to CO₂ Levels:
If PCO₂ in blood rises (hypercapnia), medullary chemoreceptors are activated, increasing respiratory rate and depth.
Rising plasma H+ levels (acidosis) activate peripheral chemoreceptors, prompting similar responses to enhance CO₂ elimination.
Effect of Alkalosis:
Respiratory center is depressed, decreasing respiratory rate and depth, causing CO₂ accumulation, subsequently raising H+ concentration.
Respiratory impairments can lead to acid-base imbalances:
Hypoventilation results in CO₂ retention and respiratory acidosis.
Hyperventilation results in CO₂ elimination and respiratory alkalosis.
Renal Regulation
Chemical buffers alone cannot eliminate excess acids or bases from the body:
Lungs: Eliminate volatile carbonic acid by removing CO₂.
Kidneys: Eliminate nonvolatile (fixed) acids produced by cellular metabolism (e.g., phosphoric, uric, and lactic acids, ketones) to prevent metabolic acidosis.
Kidney Functions in Acid-Base Balance:
Adjust bicarbonate levels by:
Conserving (reabsorbing) or generating new HCO₃–.
Excreting HCO₃–.
Balanced Effects: Generating or reabsorbing one HCO₃– is equivalent to losing one H+. This process drives the reaction to the left, forming H₂O (H+ converts into water).
Excreting HCO₃– results in gaining H+, thereby driving the reaction to the right.
Bicarbonate Reabsorption
Mechanism:
To maintain the alkaline reserve, kidneys must replenish bicarbonate levels.
Tubule cells lack transporters for bicarbonate but are permeable to CO₂.
Bicarbonate can re-enter the body through a transformation to CO₂.
Once in the cell, CO₂ can be reconverted into bicarbonate or released as CO₂.
Coupled Mechanism: H+ secretion is coupled to HCO₃– reabsorption, occurring in proximal convoluted tubules (PCT) and type A intercalated cells.
Steps involved are:
CO₂ + H₂O → H₂CO₃ (via carbonic anhydrase)
H₂CO₃ dissociates into H+ and HCO₃–.
H+ is actively secreted into the lumen; HCO₃– enters blood in exchange for Cl–.
H+ combines with HCO₃– to form H₂CO₃ in the filtrate.
H₂CO₃ breaks down into CO₂ + H₂O.
CO₂ diffuses back into the tubule cell.
Rate of H+ secretion adapts to ECF CO₂ levels.
New Bicarbonate Generation
Process:
H+ secreted doesn't leave the body but is incorporated into water, keeping overall HCO₃– and H+ constant.
Metabolism generates new H+ leading to acidosis, thus needing balance by generating new HCO₃–.
Mechanisms in PCT and type A intercalated cells include:
Excretion of buffered H+.
NH₄⁺ excretion, a more important mechanism for acid excretion through glutamine metabolism in PCT.
Each glutamine produces 2 NH₄⁺ and 2 new HCO₃–.
HCO₃– moves into blood while NH₄⁺ is excreted.
Bicarbonate Ion Secretion
During alkalosis, type B intercalated cells can:
Secrete HCO₃– and reclaim H+ to acidify blood.
The mechanism is opposite to bicarbonate reabsorption by type A intercalated cells, hence even during alkalosis, nephrons and collecting ducts conserve more HCO₃– than they excrete.
Abnormalities of Acid-Base Balance
Classification of Imbalances:
Acid-base imbalances fall into respiratory or metabolic categories.
Respiratory Acidosis and Alkalosis:
Caused by failure of the respiratory system to balance pH.
PCO₂ is the single most important indicator:
PCO₂ > 45 mm Hg indicates respiratory acidosis (caused by reduced ventilation, e.g., emphysema, pneumonia).
PCO₂ < 35 mm Hg indicates respiratory alkalosis (often due to hyperventilation).
Metabolic Acidosis and Alkalosis:
Metabolic acidosis indicated by low blood pH and low HCO₃–, not caused by CO₂ levels.
Causes include:
Alcohol ingestion (converts to acetic acid).
Excessive loss of HCO₃– (e.g., chronic diarrhea).
Accumulation of lactic acid, ketosis, and kidney failure.
Metabolic alkalosis indicated by rising blood pH and HCO₃–, less common than acidosis, caused by:
Vomiting of stomach contents or excessive base intake (e.g., antacids).
Effects of Acidosis and Alkalosis
Blood pH below 6.8 can depress the CNS, potentially leading to coma and death.
Blood pH above 7.8 can overexcite the nervous system, causing muscle tetany, extreme nervousness, convulsions, and death through respiratory arrest.
Compensation Mechanisms
If one physiological buffer system malfunctions, the other attempts compensation:
Respiratory Compensation:
Lungs increase or decrease breathing rate to adjust for metabolic pH problems.
Metabolic Acidosis: Increased respiratory rate and depth.
Indicators: Blood pH < 7.35, HCO₃– < 22 mEq/L, PCO₂ < 35 mm Hg.
Metabolic Alkalosis: Decreased respiratory rate to allow CO₂ accumulation.
Indicators: Blood pH > 7.45, elevated HCO₃–, PCO₂ > 45 mm Hg.
Renal Compensation:
In Respiratory Acidosis: Kidneys will reabsorb more HCO₃– and secrete more H+ to correct increasing acidity.
In Respiratory Alkalosis: Kidneys will excrete more HCO₃–.
Indicators: High pH, low PCO₂, and decreasing HCO₃– levels.
Note: Respiratory system cannot compensate for acid-base imbalances caused by lung issues, and renal system cannot compensate for imbalances caused by renal problems.