Acid/Base Balance

Acid-base balance

(H+ production = loss) •Normal plasma pH: 7.35-7.45 H+ gains: many metabolic activities produce acids •CO2 (to carbonic acid) from aerobic respiration •Lactic acid from glycolysis H+ losses and storage •Respiratory system eliminates CO2 •H+ excretion from kidneys •Buffers temporarily store H+

Protein buffer systems (in ICF and ECF)

(in ICF and ECF) •Usually operate under acid conditions (bind H+) •Binding to carboxyl group (COOH-) and amino group (—NH2) Examples: - Hemoglobin buffer system •CO2 + H2O -> H2CO3 -> HCO3- + Hb-H+ •Only intracellular system with immediate effects - Amino acid buffers (all proteins) - Plasma proteins

The events in respiratory acidosis

1. When respiratory activity does not keep pace with the rate of CO2 generation ,alveolar and plasma PCO2 increases. This upsets the equilibrium and drives the reaction to the right, generating additional H2CO3, which releases Hand lowers plasma pH 2. As bicarbonate ions and hydrogen ions are released through the dissociation of carbonic acid, the excess bicarbonate ions become part of the bicarbonate reserve. To limit the pH effects of respiratory acidosis, the excess H must either be tied up by other buffer systems or excreted at the kidneys. The underlying problem, however, cannot be eliminated without an increase in the respiratory rate.

Acid

A substance that dissociates to release H+ ions, decreasing pH

Base

A substance that dissociates to release OH- ions, increasing pH

Buffer

A substance that tends to oppose changes in a pH of a solution by removing or replacing hydrogen ions; in body fluids, buffers remain blood pH within normal limits (7.35-7.45)

Three major body buffer systems

All can only temporarily affect pH (H+ not eliminated) 1.Phosphate buffer system 2.Carbonic acid-bicarbonate buffer system 3.Protein buffer systems (in ICF and ECF)

Salt

An ionic compound consisting of a cation other than H+ and an anion other than OH-

The mechanism by free amino acids function in protein buffer systems

At the normal pH of body fluids (7.35-7.45), the carboxyl groups of most amino acids have released their hydrogen ions. If pH drops, the carboxylate ion (COO-)and the amino group (—NH2) of a free amino acid can act as weak bases and accept additional hydrogen ions, forming a carboxyl group (—COOH) and an amino ion (—NH3+), respectively. Many of the R-groups can also accept hydrogen ions, forming RH+.

BICARBONATE RESERVE

Body fluids contain a large reserve of HCO3, primarily in the form of dissolved molecules of the weak base sodium bicarbonate (NaHCO3). This readily available supply of HCO3 is known as the bicarbonate reserve.

Respiratory alkalosis

CO2 elimination at lungs outpaces CO2 generation rate Shifts bicarbonate buffer system toward generating more carbonic acid ^H+ + HCO3- -> H2CO3-> H2O + CO2 •H+ removed as CO2 exhaled and water formed Buffer system responses •Respiratory (decreased respiratory rate) •Renal (HCO3- secreted and H+ reabsorbed) •Proteins (release free H+)

The events involved in the functioning of the hemoglobin buffer system

CO2 from cellular activity is converted to carbonic acid, which quickly dissociates into bicarbonate and H+. The H+ binds to the hemoglobin molecule When we get to the lungs, we reform the carbonic acid, which can be respired.

Respiratory acidosis

CO2 generation outpaces rate of CO2 elimination at lungs Shifts bicarbonate buffer system toward generating more carbonic acid ^H2O + CO2-> H2CO3-> H+ + HCO3- •HCO3- goes into bicarbonate reserve •H+ must be neutralized by any of the buffer systems -Respiratory (increased respiratory rate) -Renal (H+ secreted and HCO3- reabsorbed) -Proteins (bind free H+)

Metabolic acidosis

Develops when large numbers of H+ are released by organic or fixed acids Accommodated by respiratory and renal responses •Respiratory response - Increased respiratory rate lowers PCO2 - H+ + HCO3- -> H2CO3 -> H2O + CO2 •Renal response - Occurs in PCT, DCT, and collecting system - H2O + CO2 -> H2CO3 -> H+ + HCO3- - H+ secreted into urine - HCO3- reabsorbed into ECF

Metabolic alkalosis

Develops when large numbers of H+ are removed from body fluids •Rate of kidney H+ secretion declines •Tubular cells do not reclaim bicarbonate •Collecting system transports bicarbonate into urine and retains acid (HCl) in ECF Accommodated by respiratory and renal responses

Fixed Acids

Do not leave solution •Remain in body fluids until kidney excretion Examples: sulfuric and phosphoric acid •Generated during catabolism of amino acids, phospholipids, and nucleic acids

pH imbalance

ECF pH normally between 7.35 and 7.45 Acidemia (plasma pH <7.35): acidosis (physiological state): •More common due to acid-producing metabolic activities Effects - CNS function deteriorates, may cause coma - Cardiac contractions grow weak and irregular (can cause s/s of heart failure) - Peripheral vasodilation causes BP drop (can cause circulatory collapse) Alkalemia (plasma pH >7.45): alkalosis (physiological state) •Can be dangerous but relatively rare

The integrated homeostatic responses to respiratory alkalosis- Decreased PCO2

HOMEOSTASIS DISTURBED- Hyperventilation causing decreased PCO2 Respiratory Alkalosis- Lower PCO2 results in a rise in plasma pH Responses to Alkalosis: Respiratory compensation- Inhibition of arterial and CSF chemoreceptors results in a decreased respiratory rate. Renal compensation- H+ ions are generated and HCO3- ions are secreted. Buffer systems other than the carbonic acid-bicarbonate system release H+ ions. Combined Effects: Increased H+ Decreased HCO3- HOMEOSTASIS RESTORED- Plasma pH returns to normal

The integrated homeostatic responses to respiratory acidosis- Increased

HOMEOSTASIS DISTURBED- Hypoventilation causing increased PCO2 Respiratory Acidosis- Elevated PCO2 results in a fall in plasma pH Responses to Acidosis: Respiratory compensation- Stimulation of arterial and CSF chemoreceptors results in increased respiratory rate. Renal compensation- H+ ions are secreted and HCO3+ ions are generated. Buffer systems other than the carbonic acid-bicarbonate system accept H+ ions. Combined Effects: Decreased PCO2 Decreased H+ and increased HCO3- HOMEOSTASIS RESTORED: Plasma pH returns to normal

The events in respiratory alkalosis

If respiratory activity exceeds the rate of CO2generation, alveolar and plasma PCO2 decline, and this disturbs the equilibrium and drives the reactions to the left, removing H+ and elevating plasma pH. As bicarbonate ions and hydrogen ions are removed in the formation of carbonic acid, the bicarbonate ions—but not the hydrogen ions—are replaced by the bicarbonate reserve.

The inverse relationship between the PCO2 and pH

PCO2 40-45mm Hg ^ pH 7.35-7.45 If PCO2 rises: H2O + CO2 -> H2CO3 -> H+ + HCO3- When carbon dioxide levels rise, more carbonic acid forms, additional hydrogen ions and bicarbonate ions are released, and the pH goes down. PCO2 ^, pH v If PCO2 falls: H+ + HCO3- -> H2CO3 -> H2O + CO2 When the PCO2 falls, the reaction runs in reverse, and carbonic acid dissociates into carbon dioxide and water. This removes H+ ions from solution and increases the pH. PCO2 v, pH ^

Organic Acids

Part of cellular metabolism •Examples: lactic acid and ketones Most metabolized rapidly so no accumulation

The responses to metabolic acidosis

Respiratory Response to Acidosis - Increased respiratory rate lowers PCO2,effectively converting carbonic acid molecules to water. Renal Response to Acidosis - Kidney tubules respond by: 1: secreting H+ ions, 2: removing CO2, and 3: reabsorbingHCO3- to help replenish the bicarbonate reserve. Other buffer systems absorb H+

respiratory and renal responses to metabolic alkalosis

Respiratory response •Decreased respiratory rate raises PCO2 •H2O + CO2-> H2CO3-> H+ + HCO3- Renal response •Occurs in PCT, DCT, and collecting system •H2O + CO2-> H2CO3-> H+ + HCO3- •HCO3- secreted into urine (in exchange for Cl-) •H+ actively reabsorbed into ECF

What is a Buffer

Substance that opposes changes to pH by removing or adding H+ Generally consists of: •Weak acid (HY) •Anion released by its dissociation (Y-) •HY -> H+ + Y- and H+ + Y- -> HY

CO2 partial pressure effects on pH

The most important factor affecting body pH •H2O + CO2-> H2CO3-> H+ + HCO3- ^Reversible reaction that can buffer body pH Adjustments in respiratory rate can affect body pH

pH

The negative exponent (negative logarithm) of the hydrogen ion (H+) concentration in a solution

The narrow range of normal pH of the ECF, and the conditions that result from pH shifts outside the normal range

The pH of the ECF (extracellular fluid) normally ranges from 7.35 to 7.45. When the pH of plasma falls below7.5, acidemia exists. The physiological state that results is called acidosis. ^Severe acidosis (pH below 7.0) can be deadly because: 1: central nervous system function deteriorates, and the individual may become comatose 2: cardiac contractions grow weak and irregular, and signs and symptoms of heart failure may develop 3: peripheral vasodilation produces a dramatic drop in blood pressure, potentially producing circulatory collapse. --- When the pH of plasma rises above 7.45, alkalemia exists. The physiological state that results is called alkalosis. ^Severe alkalosis is also dangerous, but serious cases are relatively rare.

CARBONIC ACID-BICARBONATE BUFFER SYSTEM

The primary function of the carbonic acid-bicarbonate buffer system is to protect against the effects of the organic and fixed acids generated through metabolic activity. In effect, it takes the H+ released by these acids and generates carbonic acid that dissociates into water and carbon dioxide, which can easily be eliminated at the lungs.

The major factors involved in the maintenance of acid-base balance

The respiratory system plays a key role by eliminating carbon dioxide. The kidneys play a major role by secreting hydrogen ions into the urine and generating buffers that enter the bloodstream. The rate of excretion rises and falls as needed to maintain normal plasma pH. As a result, the normal pH of urine varies widely but averages 6.0—slightly acidic. Buffer Systems- Buffer systems can temporarily store H+ and thereby provide short-term pH stability. Active tissues continuously generate carbon dioxide, which in solution forms carbonic acid. Additional acids, such as lactic acid, are produced in the course of normal metabolic operations.

Acidic

a pH below 7 is acidic; contains more H+ ions than hydroxide ions (OH-)

Classes of acids

fixed acids organic acids volatile acids

Basic

pH above 7 is basic (alkaline); more OH- ions than H+ ions

Neutral

pH of 7 - equal # of H+ and OH- (hydroxide)

Phosphate buffer system

•Buffers pH of ICF and urine

Volatile acids

•Can leave body by external respiration •Example: carbonic acid (H2CO3)

Respiratory acid-base disorders

•Imbalance of CO2 generation and elimination •Must be corrected by depth and rate of respiration changes

Carbonic acid-bicarbonate buffer system

•Most important in ECF •Fully reversible •Bicarbonate reserves (from NaHCO3 in ECF) contribute

Metabolic acid-base disorders

•Production or loss of excessive amounts of fixed or organic acids •Carbonic acid-bicarbonate system works to counter