Resting Membrane Potential Represents the period of time when excitable cells, such as nerve fibers, are not transmitting signals All body cells are electrically polarized with the inside more negatively charged than the outside Difference in charge is a result of the differences in ionic composition of the ICF(mostly K+) and ECF (mostly Na+) Concentration difference is maintained by the active transport of Na+ and K+ (sodium-potassium pump) Plasma membrane is more permeable to K+ then Na+, K+ diffuses easily from the ICF to the ECF Net result is an excess of ions inside the cell

Sodium-Potassium Pump

Blood K+ Levels Control Resting Potential

Acid–Base Balance

Understanding pH pH = a calculation based on the percentage of hydrogen (H+) ions in a solution and the amount of acids and bases Body normally maintains pH within a narrow range (7.35-7.45) Acid (by-product of metabolic processes) is defined as a compound that can dissociate and release a hydrogen ion Base is defined as a compound that can accept or combine with a hydrogen (H+) ion Calculated using the Henderson-Hasselbalch equation pH is inversely related to H+ concentration a low pH = high concentration of H+ a high pH = low concentration of H+

Understanding CO2 Metabolic by-product which diffuses from cell  tissue spaces  circulation Transported in the circulation: Dissolved in plasma (10%) exhaled through lungs As bicarbonate (70%) Attached to Hgb (20%) Combines with water to form H2CO3

Regulation of pH Chemical buffer systems in body fluid Bicarbonate buffer system Transcellular hydrogen-potassium exchange system Body proteins Lungs Changes in PCO2 and pH in the blood are sensed by brainstem and peripheral chemoreceptors which alter the respiratory rate Kidneys Hydrogen/bicarbonate exchange (secretes excess H+ and reabsorbs HCO3) Ammonia buffer system (generation of new HCO3) Phosphate buffer system (intratubular)

Buffer Systems

Laboratory Tests Arterial blood gases Assess the respiratory component of acid-base balance Serum electrolytes Base excess or deficit Measure of the bicarbonate (HCO3-) excess or deficit Anion gap Difference between serum concentration of Na+ and the sum of Cl- and HCO3- Normal range is 8 to 12 mEq/L  in lactic acidosis and diabetic ketoacidosis

Metabolic Acidosis and Alkalosis CO2 + H2O  H2CO3  H+ + HCO3− Metabolic Acidosis Metabolic Alkalosis  H+ =  pH (<7.35)  serum HCO3- RR  PCO2 and H2CO3-  H+ =  pH (>7.45)  serum HCO3- RR  PCO2

Causes of Metabolic Acidosis Increased production of metabolic acids Accumulation of lactic acid (inadequate O2 delivery, intense exercise) Ketoacidosis (uncontrolled DM, fasting or dieting) Decreased renal function Kidneys lose ability to eliminate metabolic acids and nitrogenous waste Increased bicarbonate losses loss of intestinal fluids (diarrhea, intestinal suction, fistulas) Hyperchloremic acidosis Abnormal absorption of Cl- by the kidneys Treatment with chloride containing medications

Manifestations of Metabolic Acidosis Laboratory Tests pH  HCO3 (primary)  PCO2 (compensatory)  Signs of Compensation Respiratory rate Hyperkalemia Acidic urine  Ammonia in urine GI effects Anorexia Nausea and vomiting Abdominal pain Neurological effects Weakness, lethargy Confusion, stupor, coma Cardiovascular effects Peripheral vasodilation  Cardiac output Cardiac arrhythmias Skin Warm, flushed

Causes of Metabolic Alkalosis Excess bicarbonate base Excess ingestion of bicarbonate-containing antacids (Alka-Seltzer) IV infusion of base solution (blood transfusions, TPN, LR) Loss of fixed acids Loss of acid from stomach (vomiting, gastric suction) Loss of chloride from the urine Loss of potassium (diuretics)

Manifestations of Metabolic Alkalosis Laboratory Tests pH  HCO3 (primary)  PCO2 (compensatory)  Signs of Compensation  Respiratory rate Hypoxia Respiratory acidosis Neurological effects Hyperactive reflexes Tetany Confusion Seizures Cardiovascular effects Hypotension Cardiac arrhythmias

Treatment of Metabolic Acidosis Correct the underlying cause Restoring fluid and electrolytes Correct chloride and/or potassium deficiencies NaHCO3 for normal anion gap acidosis Insulin and fluid replacement for patients in diabetic ketoacidosis

Respiratory Acidosis and Alkalosis CO2 + H2O  H2CO3  H+ + HCO3− Respiratory Acidosis Respiratory Alkalosis  H+ =  pH (<7.35)  PCO2  H2CO3-  HCO3−  H+ =  pH (>7.45)  PCO2  H2CO3-  HCO3−

Causes of Respiratory Acidosis Represents a decrease in pH caused by an elevation in PCO2 Usually due to conditions that impair alveolar ventilation such as: Acute disorders of ventilation (narcotic overdose, lung disease, chest injury, weakness or respiratory muscles or airway obstruction Chronic disorders of ventilation (COPD)-sustained increase in PaCO2 resulting in renal adaptation with marked increase in serum HCO3 and a lesser decrease in pH. Increased CO2 production (exercise, fever, sepsis, burns, CHO-rich diet)

Manifestations of Respiratory Acidosis Laboratory Tests pH  HCO3 (primary)  PaCO2 > 50 Signs of Compensation Acidic urine GI effects Anorexia Nausea and vomiting Abdominal pain Neurological effects Headache, behavioral changes Depression, paranoia Confusion, stupor, coma Tremors, paralysis Skin Warm, flushed

Treatment of Respiratory Acidosis Correct the underlying cause Directed toward improving ventilation Correct chloride and/or potassium deficiencies

Causes of Respiratory Alkalosis Systemic acid-base disorder characterized by a primary decrease in PaCO2 which produces an elevation in pH and subsequent decrease in HCO3 Causes: Hyperventilation Central stimulation of the medullary respiratory center (anxiety pain, pregnancy, sepsis, encephalitis, salicylate toxicity) Peripheral pathways of the medullary respiratory center Mechanical ventilation (if rate and volume are such that expired CO2 exceeds production

Manifestations of Respiratory Alkalosis Laboratory Tests pH  HCO3 (primary)  PCO2 (compensatory)  Signs of Compensation  Respiratory rate Hypoxia Respiratory acidosis Neurological effects Hyperactive reflexes Tetany Confusion Seizures Cardiovascular effects Hypotension Cardiac arrhythmias

Treatment of Respiratory Alkalosis Correct the underlying cause Supplemental O2 for hypoxia Adjust ventilator settings Reassurance, rebreathing and psychological support for hyperventilation syndrome