Acid-Base

Definitions Acid: substance that can donate hydrogen ions Base: substance that can accept hydrogen ions

Types of acids Carbonic acid (volatile acid, carbon dioxide,~ 15000 mmol/d). Eliminated by the lungs Non-carbonic acids (nonvolatile acids such as phosphoric and sulfuric acids, 50 -100 meq/d). Combine with buffers and subsequently excreted by the kidney

Clinical pH range pH between 7.80 and 6.80 (H+concentrations between 16 -160 neq/l) are the extremes of pH compatible with life Clinical laboratories measured pH, carbon dioxide, and oxygen in arterial samples Bicarbonate concentration can be calculated from the Henderson equation Laboratories measure total CO2 concentration (dissolved CO2 plus bicarbonate concentration, ~25-26 meq/l) in venous samples

Plasma bicarbonate concentration Laboratories measure total CO2 concentration (dissolved carbon dioxide plus bicarbonate concentration, ~25-26 meq/l) As a result, total CO2 concentration exceeds plasma bicarbonate concentration by 1.0 to 1.5 meq/l Normal plasma bicarbonate concentration is approximately 24 mEq/l

Definitions Reduced pH (elevated hydrogen ion concentration) equals acidemia Increased pH (reduced hydrogen ion concentration equals alkalemia) Process that lowers pH = acidosis Process that increases pH = alkalosis

Bicarbonate buffer system CO2 + H20  H2CO3  H+ + HCO3- If a closed system, pKa = 6.1 (normal pH= 7.40) We are an open system via the lungs excreting CO2 making this system a highly efficient buffer

Determinants of pH (pH) H+ = 24 ( CO2) (HCO3) pH must be converted to H+ (nEq/L). pH = 7.40 = 40 nEq/L 7.40 = 40 = 24 (40/24)

pH vs. [H+] [H+] 100 80 64 50 40 32 25 20 16 pH 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 [H+] = 80 – decimal digits of pH

Normals Normal pH Normal pCO2 Normal HCO3- 7.35-7.45 (7.40) 7.35-7.45 (7.40) pH = -log[H+] [H+] = 24 x pCO2/[HCO3-] Normal pCO2 36-44 mm Hg (40 mmHg) Normal HCO3- 22-26 meq/L (24 meq/l)

Metabolic Disorders Processes that directly alter bicarbonate concentration Metabolic acidosis: decreased bicarbonate Metabolic alkalosis: increased bicarbonate

Respiratory Disorders Processes that directly alter CO2 Respiratory acidosis: increased CO2 Respiratory alkalosis: decreased CO2 Buffer effect: slightly increased HCO3 with respiratory acidosis. Slightly decreased HCO3 with respiratory alkalosis.

Buffering Prevent wide changes in pH in response to the addition of base or acid Bicarbonate is the major extracellular buffer (can be easily measured) There are also intracellular buffers

Effects of Buffers on pH Bicarbonate is the major extracellular buffer. There are also intracellular buffers. The presence of buffers attenuates changes in pH in response to acid-base disorders. Immediate onset Isohydric principle (all buffers change in the same direction)

Purpose of Acid-Base Balance Maintain normal pH by buffer systems Buffer Pair H+ Acceptor H+ Donor Bicarbonate (ECFV) HCO3- H2CO3 Phosphate (urine) H2PO42- H2PO4 Ammonia (urine) NH3 NH4+ Protein

Secondary(Compensatory) Mechanisms In addition to buffering mechanisms, additional secondary (compensatory) physiologic responses occur in response to changes in pH. Invariably present in simple acid-base disorders (if not present, it is a mixed disorder)

Compensatory mechanisms The respiratory system compensates for metabolic disorders by altering CO2 (via the lungs, rapid onset, minutes) Compensation for respiratory disorders occurs by alterations in bicarbonate concentration (via the kidney, slower onset 1-2 days)

Mechanisms that Buffer an Acid Load Buffer systems (primarily bicarbonate) Extracellular fluid Immediate (HCO3- + H+ ↔ H2CO3 ↔ CO2 + H20) Increased rate and depth of breathing to decrease CO2 Lungs Minutes to hours Buffer systems (phosphate, bicarbonate, protein) Intracellular fluid 2-4 hours Hydrogen ion excretion, bicarb reabsorption, & bicarb generation Kidneys Hours to days

Summary Disorder pH HCO3- pCO2 Comment Metabolic acidosis ↓ ↓ (primary) ↓(compensatory) All 3 markers go in same direction Metabolic alkalosis   (primary)  (compensatory) Resp. acidosis  (compensatory)  (primary) pH goes opp. other 2 markers Resp. alkalosis ↓ (compensatory)

Golden rules: Simple acid-base disorders 1) PCO2 and HCO3 always change in the same direction. 2) The secondary physiologic compensatory mechanisms must be present. 3) The compensatory mechanisms never fully correct pH.

Metabolic acidosis Process that reduces plasma bicarbonate concentration Etiology: Decreased renal acid excretion Direct bicarbonate losses (GI tract or urine) Increased acid generation (exogenous or endogenous)

Causes of metabolic acidosis 1) increased acid generation Lactic acidosis, Ketoacidosis, ingestion of acids (aspirin, ethylene glycol, methanol), dietary protein intake (animal source) 2) loss of bicarbonate Gastrointestinal (diarrhea, intestinal fistulas) Renal: type 2 proximal renal tubular acidosis

Causes of metabolic acidosis 1) decreased acid excretion (impaired NH4+ excretion) Renal failure (reduced GFR) decreased ammonium excretion Type I (distal) renal tubular acidosis Type 4 renal tubular acidosis (hypoaldosteronism)

Respiratory acidosis Induced by hypercapnia (decreased alveolar ventilation) Buffering mechanisms raise plasma bicarbonate concentration (rapid but limited response, ~1-2 meq/l) Kidney minimizes the change in extracellular pH by increasing acid excretion (NH4+) generating new bicarbonate ions (delayed response, 2-3 days).

Respiratory alkalosis Reduced carbon dioxide due to increased alveolar ventilation Buffering processes lower plasma bicarbonate concentration (rapid but limited response, ~1-2 meq/l) Kidney response is to reduce net acid excretion (eliminate bicarbonate into the urine or decrease ammonium excretion). Delayed response, 1-2 days)

Respiratory disorders Acute respiratory acid base disorders always have a greater change in pH than chronic disorders Plasma Cl changes equally and inversely with plasma HCO3. Plasma anion gap does not change with respiratory disorders Plasma sodium is not directly altered by acid base disorders

Metabolic alkalosis Processes that raise plasma bicarbonate concentration Etiology: Loss of hydrogen ion from the GI tract (vomiting) or into the urine (diuretic therapy) Excessive urinary net acid excretion (primary hyperaldosteronism)

Metabolic alkalosis Urine chloride concentration: Cl responsive: urine Cl <20 meq/l (usually <10 meq/l Cl resistant: urine Cl > 20 meq/l (usuallly >50 meq/l)

Expected pH Changes for Respiratory Disorders Acute Respiratory Acidosis: HCO3- increases 1 mEq for each 10 mm increase in PCO2 Chronic Respiratory Acidosis: HCO3- increases 4 mEq for each 10 mm increase in PCO2 Acute Respiratory Alkalosis: HCO3- decreases 2 mEq for each 10 mm decrease in PCO2 Chronic Respiratory Alkalosis: HCO3- decreases 5 mEq for each 10 mm decrease in PCO2

Plasma anion gap Strong acids (HA) fully dissociate at physiologic pH (7.40) into H+ and A- H+ is buffered by HC03- A- is either excreted into the urine (normal plasma anion gap, increased plasma chloride concentration) Or, A- is reabsorbed by the kidney and retained in plasma, as an unmeasured anion (increased plasma anion gap, minimal change in plasma chloride concentration)

Renal acid excretion All of the filter of bicarbonate must be reabsorbed (primarily in the proximal tubule and loop of Henle) Final excretion of the daily acid load occurs primarily in the collecting duct (approximately 50-100 meq/d)

Titratable acidity Phosphate homeostasis is maintained by urinary excretion of dietary phosphate Monobasic phosphate is an effective urinary buffer, esp. at lower urinary pH Accounts for excretion of 10 to 40 mEq of hydrogen ion daily Cannot be increased beyond this due to the fixed amount of phosphate in urine

Ammonium excretion Contributes the major adaptive response to an acid load Can be increased in response to physiologic needs Normally 30-40 mEq/d and maximal excretion is approximately 300 mEq/d NH4+ is lipid soluble and therefore trapped in the urinary lumen

Urine anion gap An indirect estimate of urinary NH4+ excretion Urine Na + K minus urine Cl Normally, ~ 10 meq/l Becomes less positive and may even become neg with incr urinary NH4 excretion (Cl- must accomany NH4+)

Sodium and Chloride relationship Law of electroneutrality: Sodium concentration is not directly altered by acid base disorders Plasma Cl is altered in all acid base disorders (except increased plasma anion gap metaboic acidosis) Conclusion: If sodium concetration stays constant but chloride conc changes, an acid base disorder is present

Mixed Acid-base disorders The presence of more than one simple acid-base disorder simultaneously: Respiratory acidosis and metabolic acidosis (profound acidemia) Respiratory alkalosis and metabolic alkalosis (profound alkalemia) Metabolic alkalosis and respiratory acidosis Metabolic acidosis and respiratory alkalosis

Examination/quiz For this course, only simple acid-base disorders will be included in quizzes and examinations. You have got to crawl before you walk!