Overview

Conventional approaches to the diagnosis of acid-base disorders are based upon the interpretation of changes in blood pH, carbon dioxide partial pressure (PCO₂), and bicarbonate or base excess concentration. Base excess is defined as the amount of strong acid that must be added to each mL of fully oxygenated blood to return the pH to 7.40 at a temperature of 37° C and a PCO₂ of 40 mm Hg (5.3 Kilopascal [kPa]). Changes in blood pH signal either an increase (acidemia) or decrease (alkalemia) in hydrogen ion concentration and when combined with changes in PCO₂ concentration (PCO₂/pH relationship) permit the recognition of primary acid-base disturbances and the identification of respiratory and/or metabolic (nonrespiratory) disturbances (Fig. 15-1). Alternatively, the diagnosis of acid-base disorders may be determined by changes in so-called independent variables (Stewart’s approach), which includes PCO₂, strong ion (e.g., Na⁺, K⁺, C1⁻, Ca⁺², Mg⁺²) difference, and the total concentration of nonvolatile weak acid (A_TOT). The aforementioned independent variables are responsible for determining the dependent variables pH and . From a clinical standpoint, both approaches succeed in identifying acid-base disorders, although the latter (Stewart’s approach) is more enlightening, especially when mixed acid-base and electrolyte disorders co-exist. Evaluation of an animal’s acid-base status is useful for determining disease severity, diagnosing the disease, and formulating therapy.

General Considerations

I Definitions

Acid: A substance that can donate a hydrogen ion (H+): Carbonic acid (H₂CO₃) donates H+

Ex.:H2CO3→H++HCO3−

Actual bicarbonate: The amount of bicarbonate expressed in milliequivalents per liter of plasma

Anion gap: The total number of cations in the extracellular fluid equals the total number of anions; however, not all anions and cations can be measured. This means that there is an apparent “gap,” or difference, between the number of cations and the number of anions. This gap is the anion gap (AG). The AG represents the difference between unmeasured cations and unmeasured anions, the AG is mostly a result of the net negative charge on proteins, and is heavily influenced by protein concentration and is calculated as (Fig. 15-2)

AG=(Na++K+)(Cl−+HCO3−)

    Note: If a decrease in is matched by an increase in chloride, the AG does not change; the acidosis is classified as hyperchloremic or normal AG acidosis. If the decrease in HCO₃ is not accompanied by an increase in chloride concentration, the acidosis is due to the addition of unmeasured anions (e.g., lactic acidosis).

A_TOT: Total concentration of weak acid; in plasma these consist of albumin and inorganic phosphate; increases in A_TOT (weak acids) can cause metabolic (nonrespiratory) acidosis; decreases in A_TOT cause metabolic alkalosis

Base (B): A substance that can accept a hydrogen ion (H+)

Ex.:OH−+H+→H2O

AG: (Na++K+)–(Cl–+HCO3−)

Base excess (BE): The amount of base above or below the normal buffer base, expressed in milliequivalents per liter (mEq/L), in blood; positive values (+) reflect an excess of base (or deficit of acid), metabolic alkalosis; negative values (−) reflect a deficit of base (or excess of acid), metabolic acidosis

    Note: A decrease or increase of 0.1 pH unit is equal to a decrease or increase of 7 BE units when arterial carbon dioxide partial pressure (PaCO2) is 40 mm Hg and body temperature is 37° C.

Buffer: A mixture of substances in a solution that resists or reduces changes in hydrogen ion concentration (changes in pH); important buffers in the body include hemoglobin (Hb) and bicarbonate

Components of Buffering in Blood

Buffers in Whole Blood	% Buffering
Hemoglobin and oxyhemoglobin	35
Organic phosphate	3
Inorganic phosphate	2
Plasma proteins	7
Plasma bicarbonate	35
Red blood cell (RBC) bicarbonate	18
Total	100

Free water: Water without electrolytes (pure H2O); increases in plasma free water dilute plasma constituents causing dilutional acidosis; decreases in free water concentrate plasma constituents result in alkalosis

Partial pressure: The pressure an individual gas exerts on a column of mercury; expressed in millimeters of mercury (mm Hg); 1 kPa = 7.50 mm Hg; see the following example of gaseous components of air

Composition of Air

Gas	Fractional Content (%)	Partial Pressure, mm Hg (kPa)
Nitrogen (N2)	78.0 *	593 (79)
Oxygen (O2)	21.0*	159 (21)
Argon (Ar)	1.0	7 (0.9)
Carbon dioxide (CO2)	0.0	0.2
Others	0.0	0.0
Total	100	760
		(atmospheric pressure)

^*Partial pressure of water (PH₂O) varies according to humidity and has a proportionate effect on partial pressure of oxygen (PO₂) and partial pressure of nitrogen (PN₂). 1 kPa = 7.5 mm HG

pH: The negative log of the hydrogen ion (H+) concentration; the pH is inversely proportional to the log of the H+ concentration (see Fig. 15-1)

Example :(H+)=0.000001=1×10−6pH=6.0

(H+)=1×10−7pH=7.0

(H+)=1×10−8pH=8.0

Strong ion: A salt that is completely dissociated in water (e.g., Na⁺, K⁺, Cl⁻, Ca²⁺, Mg²⁺)

Strong ion difference (SID): The difference between the sums of the positive (cations) and negative (anions) strong ions; normally (Na⁺, K⁺, Cl⁻); increases in SID usually cause metabolic (nonrespiratory) alkalosis; decreases in SID usually cause metabolic (nonrespiratory) acidosis

Abnormalities in Strong Ion Difference (SID) and Total Concentration of Weak Acid (A_TOT)

SID	Increased	Metabolic alkalosis
SID	Decreased	Metabolic acidosis
ATOT	Increased	Metabolic acidosis
ATOT	Decreased	Metabolic alkalosis

Strong ion gap: Because homeostasis derives from charge balance, SIDa (apparent SID) must be counterbalanced by an equal and opposing charge termed the effective strong ion difference (SIDe). The SIDe negative charge principally stems from the dissociated moieties of plasma proteins (~78% albumin) and phosphate (~20%). The sum of these weak acids is known as A_TOT because they exist in a dissociated form (A⁻) as well as an associated form (AH). When the SIDa and SIDe are equal, the plasma pH is exactly 7.4 at a PCO₂ of 40 torr. When the SIDa and SIDe are unequal, the difference between the two is termed the strong ion gap (SIG) (SIDa–SIDe, normal = 0; Fig. 15-3). This value cannot be determined by examination of other acid-base variables or schemes, and is buried within the AG along with A⁻ and lactate.

SIDa=(Na++K+)+(2×Ca2++2×Mg2+)−(Cl−+La−)

SIDe=HCO3−+ATOT

    The SIG is similar to the AG and detects differences between unmeasured cations and unmeasured anions, but the SIG determines the difference between all positive and negative “strong ions”: ions fully dissociated at physiologic pH and buffer ions. The strong ions include: Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻, lactate, β-hydroxybutyrate, acetoacetate, and sulfate. Buffer ions include: , albumin, globulins, and phosphate. The SIG accounts for the differences between strong cations and strong anions. The simplified SIG can be estimated using albumin concentration and AG:

Dog SIG=[albumin]×4.9−AG

Cat SIG=[albumin]×7.4−AG

    Note: SIG increases in metabolic acidosis due to an addition of unmeasured strong ions (e.g., lactic acidosis, ketoacidosis)

Total CO₂ content: The amount of carbon dioxide gas extractable from plasma; total CO₂ consists of:

Bicarbonate (85% of the total CO₂ is )

Carbonic acid (10% of the total CO₂ is H₂CO₃)

CO₂ in solution

Unmeasured anions: Strong ions (anions) that are not routinely measured (e.g., lactate; PO⁴²⁺, SO⁴²⁺)

II Many factors influence an animal’s acid-base balance

A Species

B Diet (carnivorous versus herbivorous)

C Physical status

D Temperature

E Concentration of “strong” ions or salts that completely dissociate in water (e.g., Na⁺, K⁺, Cl⁻, lactic acid)

F Total protein (albumin)

G Unmeasured anions (e.g., lactic acid)

III Normal cellular metabolism continuously produces an excess of hydrogen ions, the concentration of which is regulated and eliminated by the lungs, kidneys, and gastrointestinal system to maintain an extracellular pH of approximately 7.4

A The kidneys eliminate hydrogen ions by excreting fixed acids and reabsorbing

B The lungs reduce plasma hydrogen ion concentration by eliminating CO₂

C The kidneys and gut participate in regulating pH by modulation of acid (HCl), base (Na⁺, ), and water excretion

IV Substances within the body known as buffers (see earlier table, Components of Buffering in Blood) help minimize changes in pH (e.g., hemoglobin, , , Prot⁻)

V Determination of pH and blood gases is useful in determining the animal’s acid-base status and severity of any imbalance

Formation and Elimination of Acids and Bases in Animals

I The waste products of oral intake or metabolism (aerobic or anaerobic) are mostly acidic substances that release hydrogen ions

A Volatile acid: an acid that produces a gas

H2CO3→H2O+CO2

B Nonvolatile or fixed acids: acids that cannot be converted to gas

1. Lactate + H⁺

2. Sulfate + H⁺

3. Phosphate + H⁺

II The pathways for acid removal include the kidney, lung, and gastrointestinal tract

    This is the carbonic acid equation or CO₂ hydration equation and is the basis for conventional explanations of acid-base kinetics in the body

A High-protein diets (cats, dogs, pigs, humans)

1. H⁺ excess is derived from oxidation of neutral sulfur in these amino acids

a. Methionine

b. Cystine

c. Cysteine

B Diets high in plant material and grain have excess from salts in:

1. Fatty acids (acetate, propionate)

2. Citrate (fruits)

3. Gluconates

    Example:

    Metabolizable salts of fatty acids yield after metabolism

C Based on primary dietary intake

1. Carnivores have acid urine or excess acid to excrete (pH: 5.5 to 7.5)

2. Herbivores have excess base to excrete (pH: 6 to 9) and produce alkaline urine and saliva

D Dietary and metabolic intake of acid or base equals the urinary and respiratory output, thereby maintaining the pH of the body fluids near 7.4

E Many approaches to the diagnosis and treatment of acid-base disorders are based on the following (Henderson-Hasselbalch equation):

1.  (carbonic anhydrase [CA])

2. (K; the dissociation constant for each acid)

K2K1=[H+]+[HCO3−][H2CO3]

3. 

4. Given: [CO₂] = α × PCO₂ (α = 0.0301 − solubility coefficient)

5. 

    −log (H⁺) = pH; −log K₃ = pK

    pK is that pH at which 50% of an acid or a base is in the ionized state; the pK of the acid (pK₃ = pK_a) H₂CO₃ is 6.1

6. 

pH=pK3+log⁡[HCO3−][αPCO2](Henderson-Hasselbalch eq)

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