5 Acidosis, Alkalosis, & Acid-Base Disorders

Association ↔ Dissociation H2CO3 ↔ H+ + HCO3¯ HProtein ↔ H+ + Protein¯ HA ↔ H+ + A¯ H2O ↔ H+ + OH¯ HHb ↔ H+ + Hb PO4 3¯ ↔ HPO4 2¯ ↔ H2PO4 1¯ ↔ H3PO4

Produce strong ions Completely dissociates → one way 100% dissociation; no backwards movement NaOH, NaCl, HCl, KCl, Lactic Acid, Keto Acids, Sulfate Na+ K+ Ca2+ Mg2+ NaCl → Na+ + Cl¯ HCl → Cl¯ + H+ Lactic Acid → H+ + Lactate¯ Strong acids "PUSH" the equilibria of weak acids (to protonate or associate)

Partially dissociate Able to move forwards & backwards to maintain homeostasis/equilibrium HCO3¯, H2O, HA, HProtein, H2CO3, CaProtein Plasma proteins/Hgb and PO43 ¯ HProtein ↔ H+ + Protein¯ HA ↔ H+ + A¯

= Unmeasured anions – Unmeasured cations = Weak anions (A¯) + Strong acids (SA¯) = Na+ – (Cl¯ + HCO3¯) Predicted AG = Albumin x 3 Normal range = 8-16mEq/L r/t Metabolic Acidosis Helps determine the source

= (Strong cations) – (Strong anions) = Unmeasured weak anions = (Na+ + K+ + Ca2+ + Mg2+) – (Cl¯ + Lactate) Normal range = 40-45mEq/L

AH + B ↔ BH+ + A¯ Acid + Base ↔ Conjugate acid + Conjugate base NH3 + HCl ↔ NH4+ + Cl¯ Base (NH3) accepts H+ to form conjugate acid (NH4+) Acid (HCl) donates H+ to form conjugate base (Cl¯)

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3¯

○ Myocardial and smooth muscle depression ○ Activates SNS activity in heart OR remains unchanged More drastic increase in SNS activity r/t respiratory over metabolic acidosis ○ Decreased cardiac contractility ↓CO ↓BP ○ Increased coronary perfusion in heart by affecting diastolic filing time ○ Decreased peripheral vascular resistance via arterial vasodilation ↓BP ○ Increased cerebral blood flow d/t cerebral vasodilation ↑CBF CNS metabolic effect (vascular smooth muscle cells in acidic environment) Relax and dilate Carbon dioxide = anesthetic CO2 narcosis ○ Coronary and systemic vasculature DILATE ○ Pulmonary vessels CONSTRICT during hypoxemia, hypercapnia, and acidemia Opposite effect compared to systemic vasculature High CO2 w/ elevated H+ ion concentration will cause increase in extracellular Ca2+ which causes pulmonary vasoconstriction ○ Vasculature less responsive to endogenous catecholamines - net effect less Normal pH = body hormones allow permissive effect of endogenous catecholamines (Epi and NE) work to increase HR via β1 receptor stimulation ○ Tissue hypoxia causes right shift = more O2 dropped off at the tissues Example: Increased O2 available at tissues during exercise ○ Progressive hyperkalemia Increased H+ ion causes K+ ions to move out intracellular space and into extracellular Plasma K+ increases approximately 0.6mEq/L for each 0.1 decrease in pH

○ Increased binding sites on plasma proteins for Ca2+ Decreased serum Ca2+ Respiratory and circulatory depression Neuromuscular irritability ○ Increased systemic vascular resistance ↑SVR ○ Decreased cerebral blood flow d/t cerebral vasoconstriction ↓CBF ○ Coronary and systemic vasculature CONSTRICT ○ Pulmonary vessels DILATE Decreased pulmonary vascular resistance ↓PVR Increased bronchial smooth muscle tone (bronchoconstriction) ○ Oxyhemoglobin dissociation curve left shift More difficult Hgb to release O2 at tissues ○ Hypokalemia Movement K+ ions into cells in exchange H+ ○ Hypoxic pulmonary vasoconstriction

Index that quantifies the metabolic acidosis Negative BE or “base deficit” or “acid excess” BE = Weak acid + bicarbonate BE = HCO3¯ − 24 Normal − 2 to + 2 < −2 suggests primary metabolic acidosis (base deficit or acid excess) > +2 primary metabolic alkalosis (excess base) BE also abnormal during metabolic compensation for primary respiratory disorders

Irreversible dissociation (one way →) Readily &amp; irreversibly give up H+ ions Lactic acid Hydrochloric acid (HCl) Nitric acid (HNO3) Sulfuric acid (H2SO4) Hydrobromic acid (HBr) Hydroiodic acid (HI) Perchloric acid (HClO4) Chloric acid (HClO3)

7.35-7.45 35-45 80-100 22-26

Increased strong nonvolatile acids (lactic or keto acids) concentration → no compensatory Cl¯ increase → increased anion gap Methanol intoxication Uremia Diabetic ketoacidosis Paraldehyde Isoniazid or Iron overdose (metabolism inborn error) Lactic acidosis Ethylene glycol Intoxication Salicylate intoxication

Hyperchloremic acidosis - primary HCO3¯ loss compensated w/ increased Cl¯ → unchanged anion gap Fistula (biliary, pancreatic) Ureterogastric conduit Saline administration Endocrine (Addison's, hyper-PTH) Diarrhea Carbonic anhydrase inhibitor Ammonium Renal tubular acidosis Spironolactone

Carbonic acid Phosphoric acid Acetic acid HProtein Ammonium ion (NH3 conjugate acid)

H2CO3

POSITIVE Na+ K+ Ca2+ Mg2+

NEGATIVE Cl¯ Lactate¯

Logarithmic pH <7.4 ↑H+ >7.4 ↓H+ Equal change in pH = 7.2 → 7.1 H+ 16nEq/L larger increase 7.5 → 7.6 H+ 7mEq/L smaller decrease

H+ involved in nearly all biochemical reactions Component of homeostasis - affects ionization status (ion concentration equilibrium) & responsible for movement of certain molecules in & out of cells (osmolarity) Enzyme systems operate at optimal pH and variations can impact enzyme activity (Na+/K+ ATP-ase pump) Changes in ventilation, perfusion, & electrolyte composition rapidly alters H+ & acid-base balance → dynamic process w/ multiple equilibrium reactions occurring at the same time (w/in microseconds) pH & pCO2 demonstrate fairly predictable changes in many pathological conditions Alters ionization degree of proteins & drugs administered Importance out of proportion to its relatively miniscule concentration in the body

pH = 6.1 + log(HCO3¯/(PaCO2 x 0.03))

Carbonic acid Aerobic metabolism

Lactic acid Hydrogen phosphate Anaerobic metabolism

Aerobic metabolism produces volatile acids Anaerobic metabolism produces nonvolatile acids