Lecture 5: Acid-Base Balance

Arterial Blood pH Reference Range

7.35–7.45

Venous Blood pH Reference Range

7.32–7.42

Acid Definition

A substance that donates protons (H+)

Base Definition

A substance that accepts protons

Acidemia vs. Alkalemia

Acidemia is blood pH < 7.35; Alkalemia is blood pH > 7.45

Acidosis vs. Alkalosis

The underlying physiological mechanisms that cause acidemia or alkalemia

pK (or pKa)

The pH at which an acid is 50% dissociated (half-dissociated) Bicarbonate (HCO3-) Measurement Proxy :: HCO3- is the 2nd most abundant anion after Cl-; total CO2 is used as its measurement proxy

Henderson-Hasselbalch Equation

pH = 6.1 + log (HCO3- / cdCO2) or pH = 6.1 + log (HCO3- / (0.03 x PaCO2))

Henderson-Hasselbalch Components

6.1 is pK; HCO3- represents the renal component; cdCO2 (0.03 x PaCO2) represents the respiratory component

Normal Bicarbonate-to-Dissolved CO2 Ratio

20:1, yielding a log value of 1.301 and a normal blood pH of 7.40

Most Important Extracellular Buffer System

The Bicarbonate and Carbonic Acid buffer system (pK = 6.1), linking acid buffering, respiration, and renal function

Respiratory Response to Elevated CO2

Higher CO2 increases H+ and lowers pH, triggering hyperventilation to exhaling CO2 and restore pH

Phosphate Buffer System Primary Role

Minor contribution in plasma, but major buffering role intracellularly (RBCs) and for acid excretion in urine

Plasma Protein Buffer System

Albumin accounts for ~90% of non-bicarbonate plasma buffering via histidine residues (pK = 7.3)

Hemoglobin Buffer System & Chloride Shift

Hemoglobin buffers H+ inside RBCs; HCO3- trades places with Cl- between RBCs and plasma

Renal Acid Excretion Mechanisms

Na+-H+ exchange, ammonia (NH3) production/ammonium (NH4+) excretion, and dihydrogen phosphate (H2PO4-) excretion

Bicarbonate Reclamation in Kidneys

~90% of filtered HCO3- is reclaimed in the proximal tubule; capacity is exceeded when plasma HCO3- > 28 mmol/L

Primary Cause of Metabolic Acidosis

Primary decrease in plasma bicarbonate (HCO3-)

Serum Anion Gap Formula & Reference Range

AG = [Na+] - ([Cl-] + [HCO3-]); reference interval is 6–14 mmol/L representing unmeasured anions

High Anion Gap Acidosis Mnemonics

GOLD MARK (Glycols, Oxoproline, L-lactate, D-lactate, Methanol, Aspirin, Renal failure, Ketoacidosis) and MUDPILES

Ethylene Glycol vs. Propylene Glycol Toxicity

Ethylene glycol forms glycolic/oxalic acids causing urine crystals & renal failure; propylene glycol forms D- and L-lactate

Oxoproline (Pyroglutamic Acid) Cause

Chronic acetaminophen (Tylenol) use combined with malnutrition, CKD, or liver disease leading to glutathione depletion

Methanol Toxicity Consequences

Formic acid buildup causing high anion/osmolal gaps, optic papillitis, retinal edema, blindness, and coma

Aspirin (Salicylate) Toxicity Mechanism

Halts mitochondrial ATP production, forcing anaerobic metabolism (lactic acidosis) and fat burning (ketoacidosis)

Normal Anion Gap Acidosis Characteristic

Associated with hyperchloremia, caused by GI loss of HCO3- (diarrhea) or Renal Tubular Acidosis (RTA)

Type I vs. Type II Renal Tubular Acidosis (RTA)

Associated with hyperchloremia, caused by GI loss of HCO3- (diarrhea) or Renal Tubular Acidosis (RTA)

Immediate Compensation for Metabolic Acidosis

Respiratory hyperventilation to decrease CO2 and raise blood pH

Chloride-Responsive Metabolic Alkalosis

Most common type (Urine Cl < 10 mmol/L), caused by hypovolemia (vomiting, diuretics) and treated with NaCl infusion

Chloride-Resistant Metabolic Alkalosis

Urine Cl > 20 mmol/L, caused by mineralocorticoid excess (hyperaldosteronism) or glucocorticoid excess (Cushing syndrome)

Exogenous Base Causes of Alkalosis

Massive blood transfusion (citrate overload), IV bicarbonate, or excessive antacid ingestion

Respiratory Compensation Limit in Metabolic Alkalosis

Hypoventilation retains CO2, but pCO2 cannot rise above 55 mmHg due to hypoxia

Primary Cause & Compensation of Respiratory Acidosis

Caused by impaired CO2 elimination (hypercapnia); compensated immediately by blood buffers and chronically by kidneys

Primary Cause & Compensation of Respiratory Alkalosis

Caused by hyperventilation (hypocapnia); compensated by blood buffering and renal excretion of HCO3-